# DOWN SYNDROME & ALZHEIMER DISEASE--FAMILIAL AGGREGATION

> **NIH NIH R01** · INSTITUTE FOR BASIC RES IN DEV DISABIL · 1993 · $308,741

## Abstract

Alzheimer disease is the most common cause of old-age-associated
dementia, affecting as many as 2 million people. This study will
investigate the hypothesis that there are shared genetic influences on
susceptibility to Down syndrome (DS) and Alzheimer disease (AD) and will
examine heterogeneity of risk for AD among relatives of individuals with
DS. More than 90% of Down syndrome trisomies are associated with a non-
disjunction event in maternal gametes. Therefore, if there are shared
susceptibility factor(s) for AD and DS, an increased frequency  of AD
would be expected in maternal relatives for maternally derived DS cases,
compared with their paternal relatives. In addition, the occurrence of a
Down syndrome birth to a younger mother may indicate a susceptibility to
accelerated aging, expressed not only in the birth of a child with DS
but also in a higher risk for AD in her family. We hypothesize that
maternal relatives of DS probands born to younger mothers (less than 35
vs 35+ years) will be at higher risk for AD, and that their AD may be
expressed at earlier ages of onset.

We will determine DS karyotype (trisomy, translocation, mosaicism) and
identify parental origin (maternal versus paternal) of the non-
disjunction event leading to trisomy in the DS cases, using a
combination of cytogenetic and molecular polymorphism studies. We will
determine whether the frequency of AD is increased in first- and second-
degree relatives of individuals with DS compared with relatives of a
matched control group of developmentally disabled people without DS.
Ascertainment of dementia among relatives will be accomplished in two
stages. Possible cases of AD will be identified by a semi-structured
interviewed with 3 relatives of the proband. We will then evaluate the
suspected cases of AD and a random sample of all relatives by
neurological and neuropsychological examination to obtain a differential
diagnosis of dementia and by medical record review or death certificate
review. We will use lifetable analysis and logistic regression to
compare risk for AD in: 1) relatives of DS cases and relatives of
controls; 2) maternal relatives of maternally derived trisomy 21 DS
cases and their paternal relatives, and in the corresponding maternal
and paternal relatives of controls; 3) relatives of younger and older
mothers at birth of individuals with DS. If familial aggregation is
established, identification of a predisposing factor by linkage of AD
and polymorphic DNA markers in these families would be an important next
step.

## Key facts

- **NIH application ID:** 3121247
- **Project number:** 5R01AG009400-02
- **Recipient organization:** INSTITUTE FOR BASIC RES IN DEV DISABIL
- **SAM.gov UEI:** LKEPMM3KKF27
- **Principal Investigator:** NICOLE SCHUPF
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $308,741
- **Award type:** 5
- **Project period:** 1992-06-01 → 1996-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3121247

## Citation

> US National Institutes of Health, RePORTER application 3121247, DOWN SYNDROME & ALZHEIMER DISEASE--FAMILIAL AGGREGATION (5R01AG009400-02). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3121247. Licensed CC0.

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