Dataset Information

Early detection of cryptic memory and glucose uptake deficits in pre-pathological APP mice.

ABSTRACT: Earlier diagnosis and treatment of Alzheimer's disease would greatly benefit from the identification of biomarkers at the prodromal stage. Using a prominent animal model of aspects of the disease, we here show using clinically relevant methodologies that very young, pre-pathological PDAPP mice, which overexpress mutant human amyloid precursor protein in the brain, exhibit two cryptic deficits that are normally undetected using standard methods of assessment. Despite learning a spatial memory task normally and displaying normal brain glucose uptake, they display faster forgetting after a long delay following performance to a criterion, together with a strong impairment of brain glucose uptake at the time of attempted memory retrieval. Preliminary observations suggest that these deficits, likely caused by an impairment in systems consolidation, could be rescued by immunotherapy with an anti-?-amyloid antibody. Our data suggest a biomarker strategy for the early detection of ?-amyloid-related abnormalities.

SUBMITTER: Beglopoulos V

PROVIDER: S-EPMC4895343 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Early detection of cryptic memory and glucose uptake deficits in pre-pathological APP mice.

Beglopoulos V V Tulloch J J Roe A D AD Daumas S S Ferrington L L Watson R R Fan Z Z Hyman B T BT Kelly P A T PA Bard F F Morris R G M RG

Nature communications 20160601

Earlier diagnosis and treatment of Alzheimer's disease would greatly benefit from the identification of biomarkers at the prodromal stage. Using a prominent animal model of aspects of the disease, we here show using clinically relevant methodologies that very young, pre-pathological PDAPP mice, which overexpress mutant human amyloid precursor protein in the brain, exhibit two cryptic deficits that are normally undetected using standard methods of assessment. Despite learning a spatial memory tas ...[more]

PMID: 27249364

Similar Datasets

Project description:Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by a progressive cognitive decline. Epidemiological studies have suggested a protective role of caffeine consumption against age-related cognitive impairments and the risk of developing AD. Effects of caffeine have been particularly ascribed to its ability to block adenosine A2A receptors (A2ARs). Early pathological upregulation of these receptors by neurons is thought to be involved in the development of synaptic and memory deficits in AD but this remains ill-defined. To tackle this question, we employed a novel transgenic mouse model allowing to promote a neuronal upregulation of A2AR in the hippocampus of APP/PS1 mice, developing AD-like amyloidogenesis. This new model was used to determine the impact of an early upregulation of A2AR on the progression of neuropathological lesions, associated behavior and underlying mechanisms in APP/PS1 mice. Our findings revealed that the early upregulation of A2AR in the presence of an ongoing amyloid pathology exacerbates memory impairments of APP/PS1 mice. These behavioral changes were not linked to major change in the development of amyloid pathology but rather associate with an increased p-tau at neuritic plaques. Moreover, proteomic and transcriptomic analysis coupled to quantitative immunofluorescence studies indicated that neuronal impairment of the receptor promoted both neuronal- and non-neuronal autonomous alterations i.e. loss of excitatory synapses and neuroinflammatory response, respectively, both presumably accounting for the detrimental effect on memory. Overall, our results provide compelling evidence that neuronal A2AR dysfunction as seen in the brain of patients contributes to AD pathogenesis, favoring synaptic deficits promoted by both amyloid (this study) and tau lesions (our previous study). In addition to provide new insights into the complex pathophysiology of AD, the present findings underscore the potential of A2AR as a relevant therapeutic target for mitigating early synaptic loss in this neurodegenerative disorder.

Dataset Information

Early detection of cryptic memory and glucose uptake deficits in pre-pathological APP mice.

Publications

Early detection of cryptic memory and glucose uptake deficits in pre-pathological APP mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets