The structural integrity of anterior‐temporal and posterior‐medial brain regions in Alzheimer’s disease and Parkinson’s disease: Effects of APOEε4, p‐tau181 and Aβ42

Abstract

AbstractBackgroundAlzheimer’s disease (AD) and Parkinson’s disease (PD) are two distinct neurodegenerative brain conditions associated with varying degrees of cognitive impairment, including an overlapping amnestic phenotype. At autopsy, APOEe4 and AD proteinopathies are associated with dementia severity in both AD and PD. The extent to which in‐vivo AD biomarkers are associated with memory and underlying regional brain volume in AD and PD patients is under‐investigation. Here, we focused on plasma biomarker associations with anterior‐temporal and posterior‐medial regions that are known to accumulate tau and Aß in AD.MethodNeuroimaging, biomarker, genetic and cognitive data were collected from 244 patients through the Ontario Neurodegenerative Disease Research Initiative (MeanAge = 68.96; 41% women; 35%APOE‐e4‐carriers). Based on clinical diagnostic criteria, three groups were formed: i)AD with mild cognitive impairment or dementia(ADMCI/ADD;N = 120), ii)PD with MCI or dementia(PDMCI/PDD;N = 76) and iii)PD with normal cognition(PD‐NC;N = 48). Linear regressions assessed clinical diagnosis differences in the volumetric integrity of a priori regions: anterior‐temporal(ATN; including amygdala, fusiform gyrus, and ITG) and posterior‐medial(PMN; including PCC, parahippocampal cortex and precuneus;Fig1). Differences on related item recognition memory and associative memory was examined via the FaceName Association Task. APOE(e4‐/e4+), p‐tau181‐UGOT and Aß42 associations between ATN/PMN and item recognition/associative memory outcomes were estimated. Diagnostic*APOEe4*ptau181 interactions were tested. Age, sex, education and ICV were covaried.ResultBackground characteristics showed that the ADMCI/ADD group exhibited the oldest age and the highest frequency of female sex and e4‐carriership. ADMCI/ADD and PDMCI/PDD, but not PD‐NC, exhibited elevated ptau181 and Aß42 relative to a healthy control group. Both ADMCI/ADD and PDMCI/PDD groups exhibited PMN and ATN degradation, as well as memory impairment, relative to the PD‐NC(Fig2A‐B). Plasma p‐tau181 was associated with ATN and PMN, as well as associative memory(Fig3A). APOEe4 was associated with PMN only, as well as item recognition(Fig3B). Diagnostic*APOEe4*ptau181 interactions were not significant. Post‐hoc analysis showed significant p‐tau181xAPOEe4 interactions on item recognition and total white matter hyperintensity(WMH;Fig3C). Aß42 was not associated with outcomes.ConclusionVolumes of the ATN and PMN are lower in cognitively impaired AD and PD patients with higher p‐tau and/or APOEe4‐carriership. P‐tau and APOEe4 may work synergistically to promote domain‐specific memory impairment and WMH burden in both AD and PD.