Citation

Panza F, Lozupone M, Bellomo A, Imbimbo BP. Ageing Res. Rev. 2019; 55: e100948.

Copyright

(Copyright © 2019, Elsevier Publishing)

DOI

10.1016/j.arr.2019.100948

PMID

31454563

Abstract

In the Alzheimer's disease (AD) brain, accumulation of the amyloid-β (Aβ) peptide starts 15-20 years before clinical symptoms become apparent and is believed to be the initial event of the pathological process. Unfortunately, candidate drugs targeting production, clearance and deposition of Aβ have failed to show clinical benefit in patients with established or prodromal disease, or in cognitively normal subjects with high risk of developing AD. Surprisingly, several potent anti-Aβ drugs accelerated cognitive decline of AD and, in some cases, worsened neuropsychiatric symptoms (NPS) and triggered suicidal ideation. Clarifying the relationships between the AD-related pathology and NPS of AD patients may be useful for elucidating the underlying pathophysiological process. We believe that steady overproduction of Aβ in AD may represent an attempt of the brain to mitigate or repair neuronal damage/insult. Sudden reductions of brain Aβ levels with potent anti-Aβ drugs may worsen cognition and exacerbate NPS.

Language: en

Keywords

Humans; Animals; Suicidal Ideation; Suicidal ideation; Dementia; Brain; Alzheimer Disease; Neuropsychiatric symptoms; Lifestyle; Cognitive Dysfunction; Nootropic Agents; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Anti-Aβ drugs; Drug side effects