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Review
. 2025 Jan 6;40(1):86.
doi: 10.1007/s11011-024-01507-4.

Resilience mechanisms underlying Alzheimer's disease

Chu Shi Chew  1 , Jia Yee Lee  1 , Khuen Yen Ng  2 , Rhun Yian Koh  3 , Soi Moi Chye  4
Affiliations
Review

Resilience mechanisms underlying Alzheimer's disease

Chu Shi Chew et al. Metab Brain Dis. .

Abstract

Alzheimer's disease (AD) consists of two main pathologies, which are the deposition of amyloid plaque as well as tau protein aggregation. Evidence suggests that not everyone who carries the AD-causing genes displays AD-related symptoms; they might never acquire AD as well. These individuals are referred to as non-demented individuals with AD neuropathology (NDAN). Despite the presence of extensive AD pathology in their brain, it was found that NDAN had better cognitive function than was expected, suggesting that they were more resilient (better at coping) to AD due to differences in their brains compared to other demented or cognitively impaired patients. Thus, identification of the mechanisms underlying resilience is crucial since it represents a promising therapeutic strategy for AD. In this review, we will explore the molecular mechanisms underpinning the role of genetic and molecular resilience factors in improving resilience to AD. These include protective genes and proteins such as APOE2, BDNF, RAB10, actin network proteins, scaffolding proteins, and the basal forebrain cholinergic system. A thorough understanding of these resilience mechanisms is crucial for not just comprehending the development of AD but may also open new treatment possibilities for AD by enhancing the neuroprotective pathway and targeting the pathogenic process.

Keywords: AD neuropathology; Alzheimer’s disease; Molecular pathways; Resilience mechanisms.

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Conflict of interest statement

Declarations. Ethical approval: This article does not contain any studies with human participants or animals performed by any of the authors. Consent to participate: Not applicable. Competing interests: The authors declare no competing interests.

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