Spastic paraplegia preceding <i>PSEN1</i>-related familial Alzheimer's disease.

ABSTRACT:

Introduction

We investigated the frequency, neuropathology, and phenotypic characteristics of spastic paraplegia (SP) that precedes dementia in presenilin 1 (PSEN1) related familial Alzheimer's disease (AD).

Methods

We performed whole exome sequencing (WES) in 60 probands with hereditary spastic paraplegia (HSP) phenotype that was negative for variants in known HSP-related genes. Where PSEN1 mutation was identified, brain biopsy was performed. We investigated the link between HSP and AD with PSEN1 in silico pathway analysis and measured in vivo the stability of PSEN1 mutant γ-secretase.

Results

We identified a PSEN1 variant (p.Thr291Pro) in an individual presenting with pure SP at 30 years of age. Three years later, SP was associated with s

SUBMITTER: Chelban V 

PROVIDER: S-EPMC8088589 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature