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Study Description

Multiplex Family Study
The purpose of the NIA Genetics Initiative: Multiplex Family Study is to identify families with multiple members diagnosed with late-onset Alzheimer's Disease. Families will be characterized clinically and blood samples will be collected to establish cell lines. If a blood sample is not available, autopsy samples will be collected for DNA extraction and storage. Our goal is to recruit 1,000 families over the course of the study. Clinical and demographic data from these families will be collected at the local site and coded data, without identifiers, will be sent and included in a national database of families with Alzheimer's Disease. This database, along with the biological samples, will be housed at the National Cell Repository for Alzheimer's Disease (NCRAD) at Indiana University. The Center or provider and the Cell Repository must sign a Material Transfer Agreement for shipment of biological samples and phenotypic data to NCRAD. The biological samples and data from these families will be available to qualified researchers, who must sign a Material Transfer Agreement before receiving DNA and data. An oversight committee known as the Cell Bank Advisory Committee (CBAC) will review and monitor the process of family identification and enrollment, data collection, the establishment of cell lines and access to samples.

The first 362 families of the Multiplex Family Study (including 2,105 family members) were included in a 6K SNP genome-wide scan at the NIH-supported, Center for Inherited Disease Research (CIDR). An additional 297 unrelated, healthy controls were also genotyped at CIDR. The average age of onset of AD in the genotyped sample is 74 years and 62% of the sample is women. While primarily Caucasian, 3% are African-American, and 3% are of Hispanic ancestry. 72% of the families had at least 2 affected siblings, whereas 21% had 3 or more sampled affected individuals and 7% had 4 or more genotyped, affected family members.

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Publicly Available Data (Public ftp)

Connect to the public download site. The site contains release notes and manifests. If available, the site also contains data dictionaries, variable summaries, documents, and truncated analyses.

Study Inclusion/Exclusion Criteria

Families: There must be three individuals in the family for which biological samples are available.

  1. Proband:
    • A diagnosis of Definite (autopsy confirmed) AD (Alzheimer's Disease) by established neuropathological criteria or Probable AD by NINCDS-ADRDA criteria
    • Age at onset (AAO) or age at diagnosis of > 60 years
    • Individual was evaluated in person and diagnosed by an NIA-funded Alzheimer's Disease Center/approved institution or by staff associated with the Center/institution; or the autopsy was done at an Alzheimer's Disease Center/approved institution
    • Biological samples available (see 4. Biological Samples)
  2. Second Family Member:
    • A sibling of the proband
    • A diagnosis of Definite AD, Probable AD, or Possible AD by NINCDS-ADRDA criteria
    • AAO or age at diagnosis > 60 years
    • Preferred that individual be evaluated in person, but a diagnosis by medical records and telephone interview is acceptable
    • Biological samples available (see 4. Biological Samples)
  3. Third Family Member:
    • A sibling, half-sibling, parent, offspring, aunt, uncle, niece/nephew, or first cousin of the proband
    • A diagnosis of Definite AD, Probable AD, Possible AD by NINCDS-ADRDA criteria; a less definitive diagnosis of questionable dementia; MCI (Mild Cognitive Impairment); or unaffected
    • If affected, AAO of dementia or age at diagnosis > 50 years
    • If unaffected, must be > 60 years
    • Preferred that the individual be evaluated in person, but a diagnosis by medical records and telephone interview (affected) or telephone interview (unaffected) is acceptable
    • Biological samples available (see 4. Biological Samples)
  4. Biological Samples:
    • Fresh blood
    • Immortalized cell lines
    • Autopsy material: 3 to 5 grams of FROZEN cortex, fixed samples are not acceptable


  • The minimum age for controls is 60.
  • Controls are defined as individuals without subjective complaints of memory loss or cognitive decline and whose neuropsychological test performance falls within the range of norms for age and education.
  • The absence of cognitive impairment must have been documented within the last year either by neuropsychological testing or semiquantitative neurological or psychiatric examination.
  • Controls should not have a history of major neurological or psychiatric disorders and no life-threatening conditions.
  • Controls should not have a current diagnosis of schizophrenia, bipolar disorder, major depression, OCD, anxiety/panic disorder.
  • Controls should not have a current diagnosis or history of PD, AD, MS, brain tumor, and HD.
  • No 1st degree relatives of individuals diagnosed with dementia can qualify as controls. 2nd and 3rd degree relatives are acceptable.
  • The control can be a spouse of a proband (or the spouse of a proband's siblings) unless his/her offspring have been included in the family ascertainment and has been diagnosed with AD. Up to 50% of the controls could be spouses of the cases in the NIA LOAD study.

Molecular Data
TypeSourcePlatformNumber of Oligos/SNPsSNP Batch IdComment
Linkage Array Illumina Linkage-IVb Marker Panel 6090 N/A
Study History

In 2002, the National Institutes on Aging (NIA) Genetics Initiative for Late-Onset Alzheimer's Disease (LOAD) was launched to expand the available resources for studies to identify the genes contributing to Alzheimer's disease (AD). The NIA-LOAD Multiplex Family Study is a major component of the initiative. NIA-LOAD is a multi-center study recruiting families with two or more affected siblings clinically or pathologically diagnosed with AD. Each Alzheimer's Disease [Research] Centers (ADCs) have been responsible for recruitment and examination using a uniform protocol. The National Cell Repository for AD (NCRAD) at Indiana University has been responsible for creating lymphoblastoid cell lines and storing clinical information from each family. The NCRAD advisory board currently oversees distribution of clinical information and DNA to qualified genetic researchers.

Selected publications
Diseases/Traits Related to Study (MESH terms)
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