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. 2006 Apr 5;15(1):66–71. doi: 10.1111/j.1750-3639.2005.tb00101.x

Intracellular and Extracellular Aβ, a Tale of Two Neuropathologies

A Claudio Cuello 1,✉
PMCID: PMC8095923  PMID: 15779238

Abstract

The central pathological cause of Alzheimer disease (AD) is hypothesized to be an excess of β‐amyloid (Aβ) which accumulates into toxic fibrillar deposits within extracellular areas of the brain. These deposits disrupt neural and synaptic function and ultimately lead to neuronal degeneration and dementia. In addition to the pathological roles attributed to Aβ, evidence from our laboratory would suggest that Aβ serves a physiological role in the modulation of CRE‐directed gene expression. This commentary also highlights some of the pathological consequences of the accumulation of intracellular Aβ. Finally it discusses the impact of cortical Aβ burden on transmitter‐specific synaptic numbers as well as the generation of dystrophic neurites. The fundamental thesis of my proposal is that the Aβ pathology seen in AD is a continuous process from an initial abnormal Aβ intracellular accumulation to the well‐established extracellular Aβ aggregation, culminating in the formation of amyloid plaques and dystrophic neurites.

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