Putative pathological mechanisms of late-life depression and Alzheimer's disease.

Autor: Hasan SMN; Department of Psychology, Memorial University of Newfoundland and Labrador, Newfoundland and Labrador, A1B3Xs, Canada. Electronic address: smnhasan@mun.ca., Clarke C; Department of Psychology, Memorial University of Newfoundland and Labrador, Newfoundland and Labrador, A1B3Xs, Canada., Strand T; Department of Psychology, Memorial University of Newfoundland and Labrador, Newfoundland and Labrador, A1B3Xs, Canada., Bambico FR; Department of Psychology, Memorial University of Newfoundland and Labrador, Newfoundland and Labrador, A1B3Xs, Canada. Electronic address: fbambico@mun.ca.
Jazyk: angličtina
Zdroj: Brain research [Brain Res] 2023 Aug 15; Vol. 1813, pp. 148423. Date of Electronic Publication: 2023 May 25.
DOI: 10.1016/j.brainres.2023.148423
Abstrakt: Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by progressive impairment in cognition and memory. AD is accompanied by several neuropsychiatric symptoms, with depression being the most prominent. Although depression has long been known to be associated with AD, controversial findings from preclinical and clinical studies have obscured the precise nature of this association. However recent evidence suggests that depression could be a prodrome or harbinger of AD. Evidence indicates that the major central serotonergic nucleus-the dorsal raphe nucleus (DRN)-shows very early AD pathology: neurofibrillary tangles made of hyperphosphorylated tau protein and degenerated neurites. AD and depression share common pathophysiologies, including functional deficits of the serotonin (5-HT) system. 5-HT receptors have modulatory effects on the progression of AD pathology i.e., reduction in Aβ load, increased hyper-phosphorylation of tau, decreased oxidative stress etc. Moreover, preclinical models show a role for specific channelopathies that result in abnormal regional activational and neuroplasticity patterns. One of these concerns the pathological upregulation of the small conductance calcium-activated potassium (SK) channel in corticolimbic structure. This has also been observed in the DRN in both diseases. The SKC is a key regulator of cell excitability and long-term potentiation (LTP). SKC over-expression is positively correlated with aging and cognitive decline, and is evident in AD. Pharmacological blockade of SKCs has been reported to reverse symptoms of depression and AD. Thus, aberrant SKC functioning could be related to depression pathophysiology and diverts its late-life progression towards the development of AD. We summarize findings from preclinical and clinical studies suggesting a molecular linkage between depression and AD pathology. We also provide a rationale for considering SKCs as a novel pharmacological target for the treatment of AD-associated symptoms.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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