Maternal family history is associated with Alzheimer's disease biomarkers.
A family history of Alzheimer's disease (AD) increases one's risk of developing late-onset AD (LOAD), and a maternal family history of LOAD influences risk more than a paternal family history. Accumulating evidence suggests that a family history of dementia associates with AD-typical biomarker changes. We analyzed cross-sectional data from non-demented, mild cognitive impairment (MCI), and LOAD participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) with PET imaging using Pittsburgh Compound B (PiB, n = 99) and cerebrospinal fluid (CSF) analysis (n = 403) for amyloid-β peptide (Aβ) and total tau. We assessed the relationship of CSF and PiB biomarkers and family history of dementia, as well as parent gender effects. In the larger analysis of CSF biomarkers, we assessed diagnosis groups individually. In the overall sample, CSF Aβ, tau/Aβ ratio, and global PiB uptake were significantly different between family history positive and negative groups, with markers of increased AD burden associated with a positive maternal family history of dementia. Moreover, a maternal family history of dementia was associated with significantly greater PiB Aβ load in the brain in the parietal cortex, precuneus, and sensorimotor cortex. Individuals with MCI positive for a maternal family history of dementia had significantly more markers of AD pathophysiology than individuals with no family history of dementia. A family history of dementia is associated with AD-typical biomarker changes. These biomarker associations are most robust in individuals with a maternal family history, suggesting that a maternally inherited factor influences AD risk.
KU Alzheimer's Disease Center, Department of Neurology, University of Kansas School of Medicine, Kansas City, KS 66160, USA. rhonea@kumc.edu
Robyn A
RA
Honea
Eric D
ED
Vidoni
Russell H
RH
Swerdlow
Jeffrey M
JM
Burns
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D000814:Aniline Compounds / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000134:cerebrospinal fluid; D060825:Cognitive Dysfunction / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000235:genetics; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009035:Mothers; D049268:Positron-Emission Tomography / Q000379:methods; D013844:Thiazoles / Q000134:cerebrospinal fluid
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D015415:Biomarkers; D013844:Thiazoles