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Alzheimer-related decrease in CYFIP2 links amyloid production to tau hyperphosphorylation and memory loss

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ABSTRACT

CYFIP2 is thought to regulate mRNA translation at synapses. Tiwari et al. reveal reduced CYFIP2 expression in post-mortem Alzheimer’s disease brains, and show that CYFIP2 reduction in mice causes abnormal amyloid production, tau hyperphosphorylation, and spatial memory loss. CYFIP2 could represent a molecular ‘hub’ with potential as a therapeutic target in Alzheimer’s disease.

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Reduced CYFIP2 expression in post-mortem Alzheimer’s disease forebrain and in a mouse model of familial Alzheimer’s disease. (A–D) CYFIP2 expression is decreased in forebrain of patients with severe Alzheimer’s disease. (A) Representative western blots. (B) CYFIP2 expression in hippocampal lysates from patients with severe Alzheimer’s disease (n = 9) and control subjects (n = 11). (C) CYFIP2 expression in lysates of STG from patients with severe Alzheimer’s disease (n = 13) and control subjects (n = 12). (D) CYFIP2 expression in hippocampal lysates of patients with mild Alzheimer’s disease (n = 12) and control subjects (n = 12). (E–G) Age-dependent decrease of CYFIP2 expression in forebrain of Tg2576 mice. (E and F) Representative western blots. (G) CYFIP2 expression in hippocampal–cortical lysates of 12-month-old wild-type mice (n = 4) and Tg2576 (n = 3). (H) CYFIP2 expression in hippocampal-cortical lysates of 4-month-old wild-type (n = 4) and Tg2576 mice (n = 4). In all panels CYFIP2 expression was normalized against NSE. Means ± standard error of the mean (SEM) are shown. *P < 0.05; **P < 0.01.
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aww205-F1: Reduced CYFIP2 expression in post-mortem Alzheimer’s disease forebrain and in a mouse model of familial Alzheimer’s disease. (A–D) CYFIP2 expression is decreased in forebrain of patients with severe Alzheimer’s disease. (A) Representative western blots. (B) CYFIP2 expression in hippocampal lysates from patients with severe Alzheimer’s disease (n = 9) and control subjects (n = 11). (C) CYFIP2 expression in lysates of STG from patients with severe Alzheimer’s disease (n = 13) and control subjects (n = 12). (D) CYFIP2 expression in hippocampal lysates of patients with mild Alzheimer’s disease (n = 12) and control subjects (n = 12). (E–G) Age-dependent decrease of CYFIP2 expression in forebrain of Tg2576 mice. (E and F) Representative western blots. (G) CYFIP2 expression in hippocampal–cortical lysates of 12-month-old wild-type mice (n = 4) and Tg2576 (n = 3). (H) CYFIP2 expression in hippocampal-cortical lysates of 4-month-old wild-type (n = 4) and Tg2576 mice (n = 4). In all panels CYFIP2 expression was normalized against NSE. Means ± standard error of the mean (SEM) are shown. *P < 0.05; **P < 0.01.

Mentions: We also studied CYFIP2 expression in the STG, which is affected to a lesser extent and at later stages than the hippocampus in Alzheimer’s disease (Braak and Braak, 1991). CYFIP2 expression was found to be significantly downregulated in severe Alzheimer’s disease STG (t = −3.28, P < 0.01; Fig. 1C), supporting our finding of reduced CYFIP2 expression in the hippocampus.Figure 1


Alzheimer-related decrease in CYFIP2 links amyloid production to tau hyperphosphorylation and memory loss
Reduced CYFIP2 expression in post-mortem Alzheimer’s disease forebrain and in a mouse model of familial Alzheimer’s disease. (A–D) CYFIP2 expression is decreased in forebrain of patients with severe Alzheimer’s disease. (A) Representative western blots. (B) CYFIP2 expression in hippocampal lysates from patients with severe Alzheimer’s disease (n = 9) and control subjects (n = 11). (C) CYFIP2 expression in lysates of STG from patients with severe Alzheimer’s disease (n = 13) and control subjects (n = 12). (D) CYFIP2 expression in hippocampal lysates of patients with mild Alzheimer’s disease (n = 12) and control subjects (n = 12). (E–G) Age-dependent decrease of CYFIP2 expression in forebrain of Tg2576 mice. (E and F) Representative western blots. (G) CYFIP2 expression in hippocampal–cortical lysates of 12-month-old wild-type mice (n = 4) and Tg2576 (n = 3). (H) CYFIP2 expression in hippocampal-cortical lysates of 4-month-old wild-type (n = 4) and Tg2576 mice (n = 4). In all panels CYFIP2 expression was normalized against NSE. Means ± standard error of the mean (SEM) are shown. *P < 0.05; **P < 0.01.
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aww205-F1: Reduced CYFIP2 expression in post-mortem Alzheimer’s disease forebrain and in a mouse model of familial Alzheimer’s disease. (A–D) CYFIP2 expression is decreased in forebrain of patients with severe Alzheimer’s disease. (A) Representative western blots. (B) CYFIP2 expression in hippocampal lysates from patients with severe Alzheimer’s disease (n = 9) and control subjects (n = 11). (C) CYFIP2 expression in lysates of STG from patients with severe Alzheimer’s disease (n = 13) and control subjects (n = 12). (D) CYFIP2 expression in hippocampal lysates of patients with mild Alzheimer’s disease (n = 12) and control subjects (n = 12). (E–G) Age-dependent decrease of CYFIP2 expression in forebrain of Tg2576 mice. (E and F) Representative western blots. (G) CYFIP2 expression in hippocampal–cortical lysates of 12-month-old wild-type mice (n = 4) and Tg2576 (n = 3). (H) CYFIP2 expression in hippocampal-cortical lysates of 4-month-old wild-type (n = 4) and Tg2576 mice (n = 4). In all panels CYFIP2 expression was normalized against NSE. Means ± standard error of the mean (SEM) are shown. *P < 0.05; **P < 0.01.
Mentions: We also studied CYFIP2 expression in the STG, which is affected to a lesser extent and at later stages than the hippocampus in Alzheimer’s disease (Braak and Braak, 1991). CYFIP2 expression was found to be significantly downregulated in severe Alzheimer’s disease STG (t = −3.28, P < 0.01; Fig. 1C), supporting our finding of reduced CYFIP2 expression in the hippocampus.Figure 1

View Article: PubMed Central - PubMed

ABSTRACT

CYFIP2 is thought to regulate mRNA translation at synapses. Tiwari et al. reveal reduced CYFIP2 expression in post-mortem Alzheimer&rsquo;s disease brains, and show that CYFIP2 reduction in mice causes abnormal amyloid production, tau hyperphosphorylation, and spatial memory loss. CYFIP2 could represent a molecular &lsquo;hub&rsquo; with potential as a therapeutic target in Alzheimer&rsquo;s disease.

No MeSH data available.


Related in: MedlinePlus