Journal Article

A curious case of early-onset dementia

Chiu, P K C, Shea, Y F, Law, C Y, Ip, W C T, Ling, T K, Lam, C W

2023

Overview

Familial AD accounts for less than 0.5% of early-onset AD cases.1 It is caused by mutations in the PSEN1, PSEN2 or APP gene, resulting in early deposition of amyloid plaques due to overproduction and deposition of Aβ42 leading to early neurodegeneration (the amyloid hypothesis).1Nonetheless a newer presenilin hypothesis suggests alternative mechanisms, eg, loss-of-function of PSEN1 with suppressed γ-secretase activity and increased Aβ42/Aβ40 ratios, resulting in neurodegeneration.2 Presenilin-1 mutations account for up to 71.5% of Asian cases of familial AD.1 These patients may have an atypical presentation such as parkinsonism or spastic paraparesis.1 With a few exceptions, familial AD mutations are considered fully penetrant with the development of dementia at a predictable age. Author contributions All authors contributed to the concept or design of the study, acquisition of the data, analysis or interpretation of the data, drafting of the manuscript, and critical revision of the manuscript for important intellectual content. Whitney CT Ip 1; YF Shea 1; TK Ling; MHKCPath2; CY Law 2; CW Lam 2,3; Patrick KC Chiu 1 1 Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, China 2 Division of Chemical Pathology, Department of Pathology, Queen Mary Hospital, Hong Kong SAR, China 3 Department of Pathology, The University of Hong Kong, Hong Kong SAR, China

• Publisher: Hong Kong Academy of Medicine
• Subject: Alzheimer's disease / Cognitive ability / Dementia / Family medical history / Genes / Genetic testing / Hospitals / Hypotheses / Mutation / Neurodegeneration / Pathology / Stroke / Tomography