Alzheimer’s Disease

Activity Around Plaques

Science Signaling  23 Sep 2008:
Vol. 1, Issue 38, pp. ec331
DOI: 10.1126/scisignal.138ec331

Identifying the underlying cellular mechanisms of cortical dysfunction in amyloid-depositing mammalian brains should hopefully generate leads in the search for effective treatments for Alzheimer’s disease. Busche et al. used in vivo two-photon calcium imaging of cortical networks to monitor Ca2+ signaling of individual layer 2/3 cortical neurons in a mouse model of Alzheimer’s disease. Fifty percent of cortical neurons in diseased mice exhibited impaired functional properties. A class of “hyperactive” neurons was identified whose existence was not predicted from previous in situ or functional imaging data. The hyperactive neurons were located exclusively in peri-plaque regions, and their presence correlated with impairment of cognitive behavior. This synaptically driven hyperactivity of peri-plaque regions may underlie the increased incidence of epileptic seizures in Alzheimer’s disease patients.

M. A. Busche, G. Eichhoff, H. Adelsberger, D. Abramowski, K.-H. Wiederhold, C. Haass, M. Staufenbiel, A. Konnerth, O. Garaschuk, Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer’s disease. Science 321 1686-1689 (2008). [Abstract] [Full Text]