Genetic influences on white matter and metabolism abnormal change in Alzheimer's disease: Meta-analysis for neuroimaging research on presenilin 1 mutation

Abstract

Mutations in the presenilin1 (PSEN1) cause familial Alzheimer's disease (FAD), providing a special opportunity to study pre-symptomatic individuals who would be predicted to develop Alzheimer's disease (AD) in the future. However, whether presenilin1 (PSEN1) genotype and neuroimaging markers is a harbinger of AD remains controversial. We aimed to explore the association of PSEN1 genotype with neuroimaging markers of AD: white matter integrity, cerebral amyloid deposition and brain metabolism. We reviewed studies of diffusion tensor imaging (DTI), amyloid deposition and cerebral metabolism in patients with AD and control, in order to address the relative change of white matter microstructural associated with PSEN1 genotype. We performed a systematic meta-analysis and review of 11 cross-sectional studies identified in several database from 2008 to 2018 (n = 165). The pooled standard mean difference (SMD) value was calculated to estimate the association between PSEN1 and white matter change and brain metabolism. PSEN1 mutation carrier status was associated with mean diffusivity (MD) change (pooled SMD: 2.29; 95% CI 1.04 to 3.53; p < 0.001) and increased cerebral amyloid positron emission tomography tracer (pooled SMD: 3.78, 95% CI 1.04 to 6.53, p = 0.007). PSEN1 was not associated with white matter metabolism change (p = 0.069). PSEN1 was associated with mean diffusivity (MD) increase in DTI markers and decreased brain metabolism. Theses associations may suggest the potential role of the PSEN1 gene and imaging marker in Alzheimer's disease.

Keywords: Alzheimer’s disease; Imaging marker; Mean diffusivity; Metabolism change; Presenilin1; White matter integrity.