Of mice and men: The relevance of transgenic mice Abeta immunizations to Alzheimer's disease.

Abstract

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder characterized by a time-dependent amyloid fibril deposition in cortical senile plaques and cerebral vascular walls. Several transgenic (Tg) mice have been engineered to overexpress amyloid-beta precursor protein (AβPP) with familial AD mutations. With advancing age, the Tg mice accumulate amyloidbeta (Aβ) peptides, primarily of 40 to 42 amino acids, in plaques and blood vessel wall deposits which resemble morphologically those characteristic of AD. Immunizing Tg mice with Aβ peptides or infusion of antiAβ antibodies resulted in a remarkable Aβ load decrease and reversal of cognitive dysfunction in these animals [1–4]. These observations led to immediate efforts to employ similar therapeutic protocols in AD patients. However, Tg hAβPP-overexpressing mice differ from AD patients in several important biochemical, anatomical, pathological and temporal aspects. These fundamental differences must be considered when extrapolating Tg mice Aβ vaccination experimental observations to AD. It is now clear that the amyloid deposits of Tg mice chemically characterized to date are not necessarily