PMID:10188929

Citation	Dawson, GR, Seabrook, GR, Zheng, H, Smith, DW, Graham, S, O'Dowd, G, Bowery, BJ, Boyce, S, Trumbauer, ME, Chen, HY, Van der Ploeg, LH and Sirinathsinghji, DJ (1999) Age-related cognitive deficits, impaired long-term potentiation and reduction in synaptic marker density in mice lacking the beta-amyloid precursor protein. Neuroscience 90:1-13
Abstract	Mutations in the beta-amyloid precursor protein are strongly associated with some cases of familial Alzheimer's disease. The normal physiological role of beta-amyloid precursor protein in the brain was evaluated in a cross-sectional analysis of mice deficient in beta-amyloid precursor protein. Compared with wild-type control mice the beta-amyloid precursor protein-null mice developed age-dependent deficits in cognitive function and also had impairments in long-term potentiation. In addition, the brains of the beta-amyloid precursor protein-null mice had marked reactive gliosis in many areas, especially in the cortex and hippocampus. A subpopulation of mice (n = 15) died prematurely (between three and 18 months of age). Analysis of another six mice from the same population that were showing weight loss and hypolocomotor activity exhibited a marked reactive gliosis as detected by immunoreactivity for glial fibrillary acidic protein and a profound loss of immunoreactivities for the presynaptic terminal vesicle marker proteins synaptophysin and synapsin and the dendritic marker microtubule-associated protein-2 in many brain areas, but most predominantly in the cortex and hippocampus. These results suggest that normal beta-amyloid precursor protein may serve an essential role in the maintenance of synaptic function during ageing. A compromise of this function of the beta-amyloid precursor protein may contribute to the progression of the memory decline and the neurodegenerative changes seen in Alzheimer's disease.
Links	PubMed
Keywords	Aging/psychology; Alzheimer Disease/metabolism; Amyloid beta-Protein Precursor/deficiency; Amyloid beta-Protein Precursor/genetics; Amyloid beta-Protein Precursor/physiology; Animals; Avoidance Learning; Biological Markers; Cerebral Cortex/chemistry; Cerebral Cortex/pathology; Cognition Disorders/genetics; Disease Models, Animal; Glial Fibrillary Acidic Protein/analysis; Gliosis/genetics; Hippocampus/chemistry; Hippocampus/pathology; Long-Term Potentiation/genetics; Male; Maze Learning; Mice; Mice, Knockout; Microtubule-Associated Proteins/deficiency; Receptors, Presynaptic/chemistry; Synapsins/deficiency; Synaptophysin/deficiency
edit table

Annotations

Gene product	Qualifier	GO ID	GO term name	Evidence Code	with/from	Aspect	Notes	Status
edit table

References

See Help:References for how to manage references in GONUTS.