Coexisting cholinergic and parahippocampal degeneration: a key to memory loss in dementia and a challenge for transgenic models?
One century after Alzheimer's initial report, a variety of animal models of Alzheimer's disease (AD) are being used to mimic one or more pathological signs viewed as critical for the evolution of cognitive decline in dementia. Among the most common are, (a) traditional lesion models aimed at reproducing the degeneration of one of two key brain regions affected in AD, namely the cholinergic basal forebrain (CBF) and the transentorhinal region, and (b) transgenic mouse models aimed at reproducing AD histopathological hallmarks, namely amyloid plaques and neurofibrillary tangles. These models have provided valuable insights into the development and consequences of the pathology, but they have not consistently reproduced the severity of memory deficits exhibited in AD. The reasons for this lack of correspondence with the severity of expected deficits may include the limited replication of multiple neuropathology in potentially key brain regions. A recent lesion model in the rat found that severe memory impairment was obtained only when the two traditional lesions were combined together (i.e. conjoint CBF and entorhinal cortex lesions), indicative of a dramatic impact on cognitive function when there is coexisting, rather than isolated, damage in these two brain regions. It is proposed that combining AD transgenic mouse models with additional experimental damage to both the CBF and entorhinal regions might provide a unique opportunity to further understand the evolution of the disease and improve treatments of severe cognitive dysfunction in neurodegenerative dementias.
LINC UMR 7191, Université Louis Pasteur, CNRS, Institut Fédératif de Recherche IFR 37, GDR CNRS 2905, Strasbourg, France. jean-christophe.cassel@linc.u-strasbg.fr
Jean-Christophe
JC
Cassel
Chantal
C
Mathis
Monique
M
Majchrzak
Pierre-Henri
PH
Moreau
John C
JC
Dalrymple-Alford
D000818:Animals; D002799:Cholinergic Fibers / Q000473:pathology; D003704:Dementia / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000473:pathology; D008569:Memory Disorders / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000235:genetics / Q000473:pathology*; D016548:Prosencephalon / Q000473:pathology