Linkage and association of preserved cognitive function in the midwestern Amish at a higher genetic risk of Alzheimer's disease.

Introduction: Genetic factors promoting cognitive preservation in high-risk older adults for Alzheimer's disease (AD) risk remain understudied. Among Midwestern Amish with elevated AD genetic risk, we hypothesized ranking sibships by mean genetic risk scores during linkage analysis would reveal loci influencing preserved cognition.

Methods: We evaluated 1855 Amish adults (≥75 years) using the Modified Mini-Mental Status Exam (3MS), classifying individuals with education-adjusted scores ≥87 as cognitively unimpaired (CU) and lower scores as impaired (CI).

Alzheimer's disease plasma biomarkers in the Midwestern Amish.

Introduction: Alzheimer's disease (AD) plasma biomarkers are non-invasive measures of the key amyloid beta (Aβ) and tau pathologies. Validation and generalization studies are needed to fully understand their potential for AD prediction and diagnosis in the elderly population.

Methods: In 1067 Amish individuals aged ≥ 65, we measured plasma Aβ and tau to assess their relationships with AD-related outcomes.

Heritability of Alzheimer-related plasma biomarkers in the Amish population.

Introduction: Plasma biomarkers for Alzheimer disease (AD) hold promise for disease diagnosis and prediction, yet their genetic underpinnings remain underexplored.

Methods: We measured plasma amyloid beta 40 (Aβ40), Aβ42, Aβ42/Aβ40, total tau (t-tau), phosphorylated tau 181 (p-tau181), Aβ42/t-tau, Aβ42/p-tau181, neurofilament light chain, and glial fibrillary acidic protein in the Midwestern Amish. Pedigree-based heritability was estimated from multigenerational pedigrees, and SNP-based heritability was derived from single nucleotide polymorphisms (SNPs).

Alzheimer Disease Plasma Biomarkers in the Mid-Western Amish.

Introduction: Alzheimer disease (AD) plasma biomarkers are noninvasive measures of the key amyloid beta (Aβ) and tau pathologies. Validation and generalization studies are needed to fully understand their potential for AD prediction and diagnosis in the elderly population.

Methods: In 1,067 Amish individuals aged ≥ 65, we measured plasma Aβ and tau to assess their relationships with AD-related outcomes.

Examination of MGMT as a risk gene for dementia in the Amish.

Introduction: Recently, the O-6-methylguanine-DNA methyltransferase (MGMT) locus was proposed as influencing the risk of Alzheimer's disease (AD) in women who did not carry the apolipoprotein E ε4 allele. We examined an Amish founder population for any influence of genetic variation in and around the MGMT locus on the risk for dementia.

Methods: Genetic association was performed for single nucleotide polymorphisms (SNPs) surrounding the MGMT locus.

Genetic analysis of cognitive preservation in the midwestern Amish reveals a novel locus on chromosome 2.

Introduction: Alzheimer disease (AD) remains a debilitating condition with limited treatments and additional therapeutic targets needed. Identifying AD protective genetic loci may identify new targets and accelerate identification of therapeutic treatments. We examined a founder population to identify loci associated with cognitive preservation into advanced age.

Founder population-specific weights yield improvements in performance of polygenic risk scores for Alzheimer disease in the Midwestern Amish.

Alzheimer disease (AD) is the most common type of dementia and is estimated to affect 6 million Americans. Risk for AD is multifactorial, including both genetic and environmental risk factors. AD genomic research has generally focused on identification of risk variants.

Visuospatial and Verbal Memory Differences in Amish Individuals With Alzheimer Disease and Related Dementias.

Background: Verbal and visuospatial memory impairments are common to Alzheimer disease and Related Dementias (ADRD), but the patterns of decline in these domains may reflect genetic and lifestyle influences. The latter may be pertinent to populations such as the Amish who have unique lifestyle experiences.

Methods: Our data set included 420 Amish and 401 CERAD individuals.

The genetic architecture of Alzheimer disease risk in the Ohio and Indiana Amish.

Alzheimer disease (AD) is the most common type of dementia and is currently estimated to affect 6.2 million Americans. It ranks as the sixth leading cause of death in the United States, and the proportion of deaths due to AD has been increasing since 2000, while the proportion of many other leading causes of deaths have decreased or remained constant.

Genetic variants in the SHISA6 gene are associated with delayed cognitive impairment in two family datasets.

Introduction: Studies of cognitive impairment (CI) in Amish communities have identified sibships containing CI and cognitively unimpaired (CU) individuals. We hypothesize that CU individuals may carry protective alleles delaying age at onset (AAO) of CI.

Methods: A total of 1522 individuals screened for CI were genotyped.