---
title: "Cache County Study"
id: "2346"
type: "study"
slug: "sa000014"
published_at: "2021-02-25T20:04:28+00:00"
modified_at: "2026-03-26T15:36:10+00:00"
url: "https://dss.niagads.org/studies/sa000014/"
markdown_url: "https://dss.niagads.org/studies/sa000014.md"
excerpt: "Investigators for this study report the development and use of an innovative, powerful approach to identify functional variants that provide AD resilience to high-risk individuals. In this study, pedigrees were identified with a statistical excess of AD mortality that also..."
---

## Description

Investigators for this study report the development and use of an innovative, powerful approach to identify functional variants that provide AD resilience to high-risk individuals. In this study, pedigrees were identified with a statistical excess of AD mortality that also included at least four AD high-risk resilient individuals. Linkage analysis was performed in these families and whole genome sequence (WGS) data from resilient individuals was used to interrogate identified linkage regions for candidate variants. Finally, RAB10 and SAR1A was tested for biological impact in vitro. The results of this study suggest that RAB10 variants impact risk for AD and that RAB10 may represent a promising therapeutic target for AD prevention.

Researchers user the Utah Population Database (UPDB) to identify large pedigrees with an evidence of excess AD mortality (i.e., families with a higher number of AD deaths than expected). Pedigrees with an excess of AD deaths were identified by comparing the observed (i.e., number of affected individuals in the pedigree) to the expected numbers of AD-affected individuals within the pedigree. The expected number of AD deaths was estimated using population-based, cohorts specific rates of AD death estimated from all Utah death certificates for individuals in the UPDB genealogy.

“AD resilient individuals” defined as individuals who are at least 75 years old, cognitively normal, and carry at least one APOE ε4 allele were included in this study. AD deaths were identified by the inclusion of ICD codes for AD death in individual death certificates, where deaths were only considered an AD death if the death certificate included AD ICD codes (ICD9 331.0; ICD10 F00 or G30) as a primary or contributing cause-of-death.

An expert panel of neurologists, neuropsychologists, neuropsychiatrists, and a cognitive neuroscientist assigned final diagnoses of dementia following standard research protocols (e.g., NINCDS-ADRDA criteria for AD or NINCDS-AIREN criteria for vascular dementia).

## PI

Kathleen A. Welsh-Bohmer, PhD  
 *Duke University*

John C.S. Breitner MD, MPH  
 *McGill University*

John S.K. Kauwe, PhD  
 *Brigham Young University–Hawaii*

Ron Munger PhD, MPH  
 *Utah State University*

Maria Norton, PhD  
 *Utah State University*

JoAnn Tschanz, PhD  
 *Utah State University*

## Associated Datasets

- [NG00067 - ADSP Umbrella](https://dss.niagads.org/datasets/ng00067/) This dataset includes sequencing data and harmonized phenotypes from cohorts sequenced by the Alzheimer’s Disease Sequencing Project and other AD and Related Dementia’s studies. Samples are processed using a common… [Learn more](https://dss.niagads.org/datasets/ng00067/)

## Associated Sample Sets

- [snd10014 - Cache County WGS](https://dss.niagads.org/sample-sets/snd10014/) Cache County samples were whole-genome sequenced at Illumina on the HiSeq2000 machine. BAM from hg37 build were sent to GCAD for processing on the VCPA1.1 pipeline. 207 samples passed sequencing… [Learn more](https://dss.niagads.org/sample-sets/snd10014/)

## Cohorts

- [Cache County Study (CCS)](https://dss.niagads.org/cohorts/cache-county-study-ccs/) The Cache County Study on Memory Health and Aging (CCS) was initiated in 1994 to investigate the association of APOE genotype and environmental exposures on cognitive function and dementia. This… [Learn more](https://dss.niagads.org/cohorts/cache-county-study-ccs/)

## Grants

R01-AG11380 (Cache County Study on Memory in Aging); R01-AG18712 (Cache Family Cohort Study); R01AG21136 (Cache Co. Dementia Progression Study); RF1AG054052 (Cache County Risk and Resilience Pedigrees Study).

## Acknowledgement

### Acknowledgment statement for any data distributed by NIAGADS:

Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer's Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689), funded by the National Institute on Aging.

### For investigators using Cache County Study data:

We acknowledge the generous contributions of the Cache County Memory Study participants. Sequencing for this study was funded by RF1AG054052 (PI: John S.K. Kauwe).

## Publications

- Ridge PG. **Linkage, whole genome sequence, and biological data implicate variants in RAB10 in Alzheimer's disease resilience.***Genome medicine. 2017 Nov 29.*[PubMed link](https://pubmed.ncbi.nlm.nih.gov/29183403/)