Exploratory analysis of mtDNA haplogroups in two Alzheimer's longitudinal cohorts

Abstract

Introduction Inherited mitochondrial DNA (mtDNA) variants may influence Alzheimer's disease (AD) risk. Methods We sequenced mtDNA from 146 AD and 265 cognitively normal (CN) subjects from the University of Kansas AD Center (KUADC) and assigned haplogroups. We further considered 244 AD and 242 CN AD Neuroimaging Initiative (ADNI) subjects with equivalent data. Results Without applying multiple comparisons corrections, KUADC haplogroup J AD and CN frequencies were 16.4% versus 7.6% (P = .007), and haplogroup K AD and CN frequencies were 4.8% versus 10.2% (P = .063). ADNI haplogroup J AD and CN frequencies were 10.7% versus 7.0% (P = .20), and haplogroup K frequencies were 4.9% versus 8.7% (P = .11). For the combined 390 AD and 507 CN cases haplogroup J frequencies were 12.8% versus 7.3% (P = .006), odds ratio (OR) = 1.87, and haplogroup K frequencies were 4.9% versus 9.5% (P = .010), OR = 0.49. Associations remained significant after adjusting for apolipoprotein E, age, and sex. Conclusion This exploratory analysis suggests inherited mtDNA variants influence AD risk.

CONSENSUS: A Shiny application of Dementia evaluation and reporting for the KU ADC Longitudinal Clinical Cohort Database.

“…The KU ADC Clinical Cohort is a longitudinal study involving the collection of annual clinical and neuropsychological assessments, for participants with and without dementia, [12,13,[31][32][33]. Participants enrolled in the KU ADC Clinical Cohort study receive the required NACC UDS assessments, regulated by NACC guidelines, [15-16], along with several other KU speci c items collected for site speci c research questions and to aid with operational components of the study.…”

“…A research coordinator gathers and updates demographic information, medical history, family history, and medication usage, and administers surveys related to the participants daily functioning and mood. The clinician performs a clinical interview, accompanied with a general neurological exam, to complete a clinical dementia rating scale (CDR) evaluation, [13]. Data are directly entered through the REDCap, [19] system.…”

“…Data are directly entered through the REDCap, [19] system. A Neuropsychological test battery is also performed by a trained psychometrist following a standardized testing method, [12][13]. These test scores and summary of the neuropsychological battery also follows NACC guidelines to satisfy the standard UDS 3.0 requirements, [12,15].…”

Mitophagy and the Brain

“…Offspring from maternal AD subjects show metabolic and neuroimaging changes earlier in life than offspring of paternal AD subjects [125,[149][150][151][152]. Furthermore, inherited mtDNA haplogroups are associated with both increased and decreased AD risk [153][154][155][156][157][158][159][160]. These inherited mtDNA haplogroups also interact with the nuclear DNA encoded risk factor, ApoE (apolipoprotein E) to influence AD risk [155,160,161].…”

CONSENSUS: A Shiny application of Dementia evaluation and reporting for the KU ADC Longitudinal Clinical Cohort Database.

“…These test scores and summary of the neuropsychological battery also follows NACC guidelines to satisfy the standard UDS 3.0 requirements [12], [15]. The number of variables listed for the ADC UDS requirements and the other dataset collection is further illustrated at Katelyn et al paper [14]. For Consensus reporting, we mostly utilize UDS 3.0 data from the cognitive test and CDR visits.…”