Accessing Biospecimens and Data

4RTNI-2 (4 Repeat Tauopathy Neuroimaging Initiative – Cycle 2) is a consortium of academic medical centers in partnership with patient support organizations dedicated to conducting clinical research in corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and suggestive of or variant PSP (so/vPSP) syndromes.

The goals of this study are to identify the most reliable methods for tracking CBD, PSP and so/vPSP over time, to provide information about the relative value of novel imaging techniques for diagnosis, and to evaluate the value of imaging techniques versus biomarkers in patient samples.

Study Subjects

Subjects are between 40 and 80 years old with no known neurological disease or who have corticobasal syndrome or degeneration (CBS or CBD), progressive supranuclear palsy (PSP), or suggestive of- or variant- syndromes of progressive supranuclear palsy (so/vPSP by 2017 MDS PSP Criteria). A reliable study partner is also asked to participate.

Clinical evaluations include neurological and physical examinations, interviews with the study partner, MRI scans of the brain, amyloid and tau sensitive PET scans of the brain, eye movement testing, retinal imaging, memory & thinking testing, daily-function assessments, computer-based tests of decision-making and executive abilities, collection of a detailed family history, blood and cerebrospinal fluid (CSF) collection for analysis and storage/banking, behavioral testing, speech and language evaluations, and mood questionnaires. PSP and CBD participants are seen 3 times in one year at 6-month intervals; so/vPSP and healthy participants are seen 4 times in two years.

Available Data

The comprehensive database for 4RTNI-2 includes item-level data from medical, functional, and neuropsychological evaluations, as well as diagnostic information. Datasets may be requested through 4RTNI-2; use must conform to the 4RTNI-2 Access and Publication Policy. Structural MRI data is available for a subset of participants and may be downloaded through the Laboratory for NeuroImaging at USC. A fixed minimal dataset is available through the NCRAD catalog.

Available Biospecimens

Genomic DNA, RNA, Plasma, Serum, PBMCs, CSF

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The 90+ study is a longitudinal study of aging and cognition that began in 2003 to study the oldest-old (people aged 90 years and older), the fastest growing age group in the United States. Follow the link here for more information: http://www.mind.uci.edu/research-studies/90plus-study/

Study Subjects

More than 1,600 participants are enrolled in this study and are visited every six months. NCRAD receives samples from prospectively followed subjects and has samples available for request from over 200 participants.

Available Data

Longitudinal data including demographics, family history, neuropsychological testing, neurological examination and cognitive status (normal, dementia, or cognitive impairment/no dementia). A minimal dataset is available through the NCRAD catalog and the full dataset is available by request from University of California Irvine.

Available Biospecimens

Genomic DNA

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The longitudinal Alzheimer’s Disease Neuroimaging Initiative (ADNI) is a longitudinal multi-center study that began in 2004 and is now in its fourth phase. ADNI has been validating the use of biomarkers including blood tests, tests of cerebrospinal fluid, and MRI/PET imaging for Alzheimer’s disease (AD) clinical trials and diagnosis.ADNI-3 continues to work to determine the relationships between the clinical, cognitive, imaging, genetic and biochemical biomarker characteristics of the entire spectrum of Alzheimer's disease (AD). The overall goal of the study is to continue to discover, optimize, standardize, and validate clinical trial measures and biomarkers used in AD research.

Study Subjects

This is multi-center, a non-randomized, natural history, non-treatment study. 1,070-2,000 total participants will be enrolled across three cohorts: cognitively normal (CN), mild cognitive impairment (MCI) and mild Alzheimer's Disease (AD) dementia. Participants between the ages of 55-90 (inclusive) will be enrolled at 59 sites in the United States and Canada. Approximately, 700 - 800 will be rollover participants from previous ADNI studies, and 370 - 1200 will be newly enrolled. Clinical/cognitive, imaging, biomarker, and genetic characteristics will be assessed across the three cohorts.

Available Data

ADNI maintains an unprecedented data access policy intended to encourage new investigation and to increase the pace of discovery in the race to prevent, treat, and one day cure AD. All data is made available without embargo. Armed with better knowledge of the first indications of AD from ADNI and other studies, researchers are beginning to test potential therapies at the earliest stages feasible when there may be the greatest promise for slowing down progression of this devastating disease. Researchers seeking access to ADNI data should visit USC’s Laboratory of Neuroimaging ADNI database (ADNI LONI).

Available Biospecimens

Genomic DNA, Cell Line DNA, Lymphoblastoid Cell Lines (LCLs) and RNA from blood are available for request from NCRAD.

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The African American Alzheimer’s Disease Genetics study (AA AD Genetics) is a multi-center, cross-sectional study that was established to examine genetic risk factors for Alzheimer’s disease among African Americans. The focus of the study was to provide a carefully refined phenotype, including neuropsychological test performance, cardiovascular health, and brain imaging data, for genetic association studies of AD among African Americans.

Study Subjects

The goal of the AA Genetics study was to recruit a total of 2,000 African Americans age 60 or older. Sites recruited both cases and controls, primarily from community sources and not memory clinics.

Available Data

The database includes item-level data from medical, functional, and neuropsychological evaluations, as well as diagnostic information. There is a subset of participants with structural MRI data. A fixed minimal dataset is available through the NCRAD catalog. An additional full dataset can be requested from Columbia University.

Available Biospecimens

Cell Line DNA, Lymphoblastoid Cell Lines (LCLs)

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The Alzheimer’s Biomarker Consortium – Down Syndrome (ABC-DS) is a joint study conducted by two groups of research collaborators – Neurodegeneration in Aging Down Syndrome (NiAD) and Alzheimer’s Disease in Down Syndrome (ADDS). This initiative aims to identify biomarkers that indicate Alzheimer's disease is developing or progressing and track the Alzheimer's disease process in people with Down syndrome.

Study Subjects

The NiAD sites will recruit 180 adults with DS (10% with dementia) and 40 sibling controls, age 25 years and older. The ADDS sites will recruit 200-225 adults with DS, age 40 years and older.

Available Data

The comprehensive database for ADDS and NiAD includes item-level data from medical, functional, and neuropsychological evaluations, neuroimaging data, as well as diagnostic information. Datasets may be requested through the ABC-DS committee; use must conform to the ABC-DS Data Access and Publication Policy. The complete data set is available on LONI: https://ida.loni.usc.edu/collaboration/access/appApply.jsp?project=ABCDS

Available Biospecimens

Genomic DNA, Plasma, and Serum are available from NCRAD from both cohorts.

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The Alzheimer’s Disease Researcher Centers (ADRCs) are funded at major medical institutions across the United States. Researchers at these Centers are working to translate research advances into improved diagnosis and care for people with Alzheimer’s disease while focusing on the program's long-term goal—finding a way to cure and possibly prevent Alzheimer’s.

Study Subjects

Although each center has its own area of emphasis, a common goal of the ADRCs is to enhance research on Alzheimer’s disease by creating a network that shares new ideas and research results. The clinic-based population includes subjects with Alzheimer’s disease and related disorders, as well as cognitively normal subjects and those with MCI.

Available Data

The National Alzheimer’s Coordinating Center (NACC) maintains a cumulative database including clinical evaluations, neuropathology data when available, and MRI Imaging. The NACC database comprises several standardized clinical and neuropathology data sets, all of which are freely available to the research community.

Available Biospecimens

DNA (genomic or cell line)
Plasma, serum, RNA, PBMCs, CSF from select subjects

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ARTFL (The Advancing Research and Treatment for Frontotemporal Lobar Degeneration) consortium, includes academic medical centers partnered with patient support organizations dedicated to conducting clinical research in sporadic and familial frontotemporal lobar degeneration (FLTD) syndromes.

LEFFTDS (Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects) is a longitudinal, multicenter study enrolling participants from families with known mutations in one of the three genes most commonly associated with FTLD: MAPT, GRN, and C9ORF72. This study is aimed at understanding familial frontotemporal lobar degeneration (FTLD).

The goal of both projects is to discover new biomarkers for disease activity, standardize diagnostic criteria, and identify a large group of potential participants for clinical trials of new therapeutic agents.

Study Subjects

ARTFL: Approximately 1,560 patients and family members participate in clinical evaluations including history and examination, cognitive testing, questionnaires and surveys, and collection of blood. Patients include those with FTLD syndromes such as Corticobasal Degeneration Syndrome (CBD or CBS), primary progressive aphasias (PPA) including semantic variant (svPPA) and non-fluent variant (nvPPA), behavioral variant Frontotemporal Dementia (bvFTD), Frontotemporal Dementia with Amyotrophic Lateral Sclerosis (FTD-ALS), and Progressive Supranuclear Palsy (PSP). Healthy family members of patients with genetic causes of FTLD are also enrolled.

LEFFTDS: Enrolling 300 participants from families with known mutations in microtubule associated protein tau (MAPT), GRN, and C9ORF72. Both symptomatic and asymptomatic family members are enrolled and biospecimens are collected at four annual study visits; all study visits involve clinical evaluations and cognitive testing.

Available Data

The comprehensive database for ARTFL and LEFFTDS includes item-level data from medical, functional, and neuropsychological evaluations, as well as diagnostic information. Datasets may be requested through ARTFL and LEFFTDS; use must conform to the LEFFTDS and ARTFL Data Access and Publication Policy. There is a subset of participants with structural MRI data, available for download through the Laboratory for NeuroImaging at USC. A fixed minimal dataset is available through the NCRAD catalog.

Available Biospecimens

Genomic DNA, RNA, Plasma, Serum, PBMCs, and CSF are available from both cohorts.

ARTFL has biospecimens from the baseline study visit and includes CSF from a subset of subjects.

LEFFTDS has longitudinal biospecimens from 4 study visits. All subjects are asked to provide CSF but it is not required.

All biospecimen requests undergo a formal review by the ARTFL/LEFFTDS Biospecimens and Genetics Committee. Reviews are scheduled every two months according to the following schedule:

Date of Submission	Date Reviewed (latest)
January 1-February 28	March 31
March 1-April 30	May 31
May 1 – June 30	July 31
July 1 – August 31	September 30
September 1- October 31	November 30
November 1 – December 31	January 31

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The Amyloid Neuroimaging and Genetics Initiative (ANGI) is an add-on study for people who had participated in the Imaging Dementia—Evidence For Amyloid Scanning (iDEAS) Study. The goal of the ANGI study is to pair the clinical information and brain imaging data collected in the iDEAS-Study, or other related studies, with DNA obtained from a saliva sample. ANGI participants provide a saliva sample, in which DNA is extracted and stored for future research use.

Study Subjects

ANGI is an add-on study for people who had participated in the iDEAS-Study. For the iDEAS-Study, Medicare beneficiaries, age 65 or older were enrolled over 24 months at approximately 200 sites throughout the US. Eligibility criteria for iDEAS-Study also included patients with diagnostic uncertainty after a comprehensive clinical evaluation by a dementia expert, including laboratory tests and structural brain imaging (CT or MRI). Over 1,900 iDEAS-Study participants enrolled in ANGI and provided a saliva sample.

Available Data

Slightly over 1,900 participants from the iDEAS-Study enrolled in the ANGI study. The catalog for the iDEAS-ANGI Study consists of sociodemographic data, clinical and cognitive evaluations, pre and post PET scan clinical assessments and differential diagnoses, and scan results. Additionally, the full dataset can be requested by contacting Brown University at IDEAS-ResearchPub@acr.org.

Available Biospecimens

Genomic DNA from saliva samples are available for request from NCRAD.

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The Alzheimer’s Prevention Initiative (API) Generation Program comprises two separate clinical trials, Generation Study 1 (GS1) and Generation Study 2 (GS2), that tested experimental Alzheimer’s treatments in individuals who carry one or two copies of the high-risk gene apolipoproten E ε4 (APOE4). APOE4 is estimated to be implicated in more than 50 percent of all cases of older-onset Alzheimer’s, the most common form of the disease. Though the trial was terminated before completing enrollment, the API Generation Program generated a large, shareable resource of biomaterial including blood based biomarkers, CSF and genomic material. These are available as: 1) cross-sectional aliquots from those who were successfully screened but not randomized to the trial, and 2) longitudinal aliquots from those who were randomized to the trial protocols (in varying stages of protocol completion). Follow the link here for more information.

Study Subjects

Generation Study 1: More than 900 participants were screened to qualify as cognitively unimpaired (MMSE >=24 and through memory test evaluations) males and females (post-menopausal) aged 60-75 with homozygous APOE4 genotype. More than 400 of these participants were randomized to the trial.

Generation Study 2: More than 2,500 participants were screened to qualify as cognitively unimpaired (through memory test evaluations) males and females (post-menopausal) aged 60-75 with at least one APOE4 gene. If heterozygous for APOE4, then must have elevated brain amyloid as measured by CSF Abeta or amyloid PET imaging. More than 1,000 of these participants were randomized to the trial.

Available Data

Screening and longitudinal data including demographics, neuropsychological testing, neuropsychological examination, cognitive testing, and neuroimaging data is available. A minimal dataset is available through the NCRAD catalog and the full dataset is available by request from University of Southern California Laboratory of Neuroimaging (USC LONI). Follow the link here for more information.

Available Biospecimens

Genomic DNA, Plasma, Serum, CSF

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The Dominantly Inherited Alzheimer’s Network (DIAN) is an international research partnership of leading scientists determined to understand a rare form of Alzheimer’s disease that is caused by an autosomal dominant gene mutation. Understanding this form of Alzheimer’s disease may provide clues to decoding other dementias and developing dementia treatments.

Study Subjects

Currently enrolling study participants who are biological adult children of a parent with a mutated gene (PS1, PS2, APP) known to cause dominantly inherited Alzheimer’s disease. Such individuals may or may not carry the gene themselves and may or may not have disease symptoms. This international, multi-center longitudinal study is aiming to recruit 600 individuals: 300 expected to be gene carriers who will develop AD and 300 non-demented controls (siblings).

Available Data

Participants are evaluated in a uniform manner at entry and longitudinally thereafter with instruments to include: the clinical and cognitive batteries that comprise the Uniform Data Set (UDS) and additional DIAN-specific testing. A full description is available on the DIAN website.

Available Biospecimens

Cell Line DNA, Lymphoblastoid Cell Lines (LCLs)

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The Ginkgo Evaluation of Memory Study (GEMS) is a primary prevention trial of EGb 761 120 mg twice daily versus placebo. The primary study outcome was incident dementia, with secondary outcomes of cardiovascular disease/mortality, physical function, and cognitive change/progression as related to study drug.

The study formulation and dose of Ginkgo biloba was not effective in reducing incident dementia.

Study Subjects

Between October 2000 and May 2002, 3069 non-demented subjects ages >=75 years were screened and randomized to drug or placebo at four field centers; University of Pittsburgh, Pittsburgh PA, Wake Forest University, Winston-Salem and Greensboro NC, University of California Davis, Sacramento CA, and Johns Hopkins University, Hagerstown MD. Subjects were community dwelling volunteers. Subjects underwent detailed baseline and annual cognitive testing, and those with abnormal testing underwent a neurological exam and MRI. Subjects with an incident dementia diagnosis discontinued participation and were referred for treatment. Cognitive status was known for 93.6% of all trial participants. Retention in the trial was very high (195 withdrawals, 379 deaths).

Available Data

Data collection was longitudinal until subjects reached the incident dementia endpoint, or the end of the trial. Median follow up from entry to final visit was 6.1 years. The detailed cognitive testing battery was administered at baseline and then annually beginning in 2003, with semi-annual administration of the 3MSE and CDR. A minimal dataset is available through NCRAD to approved users. The full dataset is available upon request from the GEMS Executive Committee.

Available Biospecimens

Genomic DNA, Plasma, Serum

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The Genetic Investigation in Frontotemporal Dementia and Alzheimer's disease (GIFT) study is aimed at identifying novel genes causing or altering susceptibility to Frontotemporal Dementia (FTD) and Alzheimer's disease (AD), by re-sequencing a panel of genes involved in tau metabolism in a large series of well-characterized patients with AD and FTD and controls enrolled in 6 major centers in California and Georgia.

Study Subjects

The GIFT network includes 5 centers in California (University of California at Los Angeles, San Francisco, Davis, Irvine, University of Southern California) and Emory University. Clinical data from patients enrolled at each Center are collected at the National Alzheimer's Coordinating Center (NACC) and DNA and cell lines have been collected at the National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD).

Available Data

The National Alzheimer’s Coordinating Center (NACC) maintains a cumulative database including clinical evaluations, neuropathology data when available, and MRI Imaging. The NACC database comprises several standardized clinical and neuropathology data sets, all of which are freely available to the research community.

A first set of genetic data has been deposited within the National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) and a DNA methylation dataset including a subset of GIFT study participants is available in the Gene Expression Omnibus (GEO).

Available Biospecimens

Genomic DNA, Cell Line DNA, Lymphoblastoid Cell Lines (LCLs)

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The Center for Alzheimer's Care, Imaging and Research at the University of Utah developed the Gift of Life Outpatient Autopsy Planning Program in response to an unmet need in the Intermountain West. The Program was designed to provide access to diagnostic postmortem services otherwise unavailable for families. The Program offered pre-arrangements so that a brain autopsy could be performed expeditiously to carry out the documented wishes of the family (often including the affected individual). All families documented their desire to have autopsy results and tissue shared with qualified researchers.

Study Subjects

The collection consists of specimens from 238 individuals with neurodegenerative disease enrolled in the Gift to Life Outpatient Autopsy Planning Program at the University of Utah in Salt Lake City from 2006 to 2021. Mixed source frozen tissue was provided to NCRAD for 227 individuals and whole fixed brain is available for 84 individuals. NCRAD has DNA extracted from the mixed source frozen tissue.

The NCRAD dataset lists what specimens are available for each case. Primary neuropathological diagnosis includes Alzheimer's disease in 67%, dementia with Lewy bodies in 20%, frontotemporal degeneration (FTD) in 7%, progressive supranuclear palsy in 4%, corticobasal degeneration, vascular dementia, isolated amyloid angiopathy, and tangle-only dementia are also represented. No pathological abnormalities were identified in a patient with FTD phenocopy. In addition to primary neuropathological diagnoses, details assessment of specific neuropathological features is provided in the NCRAD dataset along with the relevant comments of the neuropathologist.

Available Data

NCRAD holds detailed, anonymous extensive demographic, diagnosis, clinical and neuropathological phenotypic date. It also has copies of anonymized original autopsy reports and letters explaining to families autopsy findings and their clinical relevance. Summary fields in the NCRAD data set show what additional data are available upon request and completion of a material transfer agreement with the University of Utah. Extensive, detailed, anonymized clinical notes and test results from cognitive specialists, neuropsychologists, psychiatrists, nurse practitioners, and social workers are available for individuals seen in the clinic by application to University of Utah Health System. Results of one or more comprehensive clinical neuropsychological examinations are available for 126 cases. Most have MRI scans, many of which are acquired in 3-dimensional isovoxel protocols allowing quantitative analysis. Regionally analyzed FDG-PET data and statistical maps are available for 73.

Available Biospecimens

The Collection consists of brain specimens from 238 individuals with neurodegenerative Disease. Whole fixed brain tissue is available for 94. Extracted DNA from mixed tissue source is available from 227 subjects, 84 of which also have fixed tissue.

Neuropathological examinations are a collaboration of the Department of Pathology and ARUP laboratories at the University of Utah. It is ARUP policy to keep paraffin blocks and prepared slides from all autopsy cases indefinitely. Thus, paraffin blocks and prepared slides are available for most cases, unless the case was referred out. Slides and blocks can be obtained for review and for additional studies by contacting Dr. Mao at the University of Utah.

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Established in 1991 as a longitudinal, prospective, population-based, comparative epidemiological study of the prevalence, incidence rates, and risk factors for Alzheimer’s disease and other age associated dementias.

Study Subjects

The project enrolled community-dwelling, elderly (age >65 years) African Americans living in Indianapolis and Yoruba living in Ibadan, Nigeria, employing the same research design, methods, and investigators.

Available Data

The funding for this study ended in 2012. During the course of the study, over 8000 (n=8528) elderly African American and Yoruba participants were evaluated over a 20 year period. A fixed minimal dataset is available through the NCRAD catalog. An additional dataset can be requested through the Indianapolis Ibadan Executive Committee.

Available Biospecimens

Genomic DNA, Cell Line DNA, Lymphoblastoid Cell Lines (LCLs)

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The iPSC Initiative Study receives, processes, and distributes iPSCs and fibroblasts. Given the dramatic increase in utilization of iPSCs in AD research, it is a goal of the iPSC Initiative to provide a service of receiving iPSCs and fibroblasts to provide central expansion and characterization of lines, and prepare for distribution to relevant researchers.

Study Subjects

The lines represent a wide range of disease causing mutations, genetic risk factors, as well as sporadic AD, healthy controls and MCI.

Available Data

For subjects that are enrolled in an ADRC, the National Alzheimer’s Coordinating Center maintains a cumulative database including clinical evaluations, neuropathology data when available, and MRI imaging. The NACC database comprises several standardized clinical and neuropathology data sets, all of which are freely available to the research community. For subjects that are not enrolled in an ADRC, all available data is provided in the catalog.

Available Biospecimens

iPSCs and fibroblasts are available for request from NCRAD.

Please apply for iPSCs via the online application. The online application is internally reviewed by the Stem Cell Team on a rolling basis.

All fibroblast applications undergo a formal review by the NCRAD Biospecimens Review Committee. Please apply for fibroblasts by following the procedures for requesting NCRAD samples.

Introduction to NCRAD iPSC Initiative, Online Catalog, and Application Process

Watch this video to learn more about the NCRAD iPSC Initiative, online catalog, and application process.

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The NCRAD Family Study began in 1990 and is still actively recruiting and following subjects. Subjects are contacted annually for updates on diagnoses within their family.

Study Subjects

Families with two or more members with early or late onset AD and related dementias. Samples are obtained from affected family members and unaffected relatives (typically over age 60).

Available Data

These families are not evaluated in person and all clinical information is obtained through telephone and medical record review. Therefore, data is limited to the following: family history; demographic data; medical records on the evaluation; diagnosis and treatment of symptomatic subjects; telephone cognitive batter; neuropathological findings when available.

Available Biospecimens

Genomic DNA, Cell Line DNA, Lymphoblastoid Cell Lines (LCLs), PBMCs, Fixed Brain Tissue, Frozen Brain Tissue

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The NIA Genetics Initiative/NIA-AD FBS Study is a multi-site study initiated in 2002 with the purpose of identifying families with multiple members diagnosed with late-onset Alzheimer’s Disease (LOAD). Autopsy is offered to all active study subjects.

Study Subjects

The study requires at least two full siblings with late onset Alzheimer’s disease (symptoms developed after age 60) and a third family member who is either: 1) affected and over age 50; or 2) unaffected and over age 60. In addition, a control cohort was also enrolled. These subjects were enrolled over the age of 60 with no neurological problems such as Alzheimer’s disease, Parkinson’s disease or stroke and have no parents, children or siblings with Alzheimer’s disease.

Available Data

Enrolled family members complete a study visit (in person or by telephone).

Study subjects are followed longitudinally and complete a study visit approximately every 2 years.

The catalog for the NIA-AD FBS Study consists of a subset of variables that can be used to better understand the dataset and perform initial feasibility studies. Sites submit study data quarterly to the study data coordinating center located at Columbia University. This catalog is then updated quarterly after data cleaning is complete. Additional data can be requested from Columbia University:

LOAD Data Request/Manuscript Proposal

Available Biospecimens

Genomic DNA, Cell Line DNA, Lymphoblastoid Cell Lines (LCLs)

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