Dataset Information

Early Cognitive and Behavioral Deficits in Mouse Models for Tauopathy and Alzheimer's Disease.

ABSTRACT: Neurocognitive disorders, among which Alzheimer's disease (AD), have become one of the major causes of death in developed countries. No effective disease-modifying therapy is available, possibly because current treatments are administered too late to still be able to intervene in the disease progress. AD is characterized by a gradual onset with subclinical neurobiological and behavioral changes that precede diagnosis with years to even decades. The earlier the diagnosis, the earlier potential treatments can be tested and started. Mouse models are valuable to study the possible causes underlying early phases of neuropathology and their reflection in behavior and other biomarkers, to help improve preclinical detection and diagnosis of AD. Here, we assessed cognitive functioning and social behavior in transgenic mice expressing tau pathology only (Tau-P301L) or a combination of amyloid and tau pathology [amyloid precursor protein (APP)-V717I × Tau-P301L]. The mice were subjected to a variety of behavioral tasks at an age of 3-6 months, i.e., at an early phase of their AD-like pathology. We hypothesized that compared to age-matched wild-type controls, transgenic mice would show specific impairments in both cognitive and non-cognitive tasks. In line with our expectations, transgenic mice showed decreased cognitive flexibility in the Morris water maze, decreased exploratory behavior, decreased performance in a nesting task, and increased anxiety-like behavior. In accordance with the amyloid-cascade hypothesis, some of the behavioral measures showed more severe deficits in APP-V717I × Tau-P301L compared to Tau-P301L mice, indicating an exacerbation of disease processes due to the co-occurrence of amyloid and tau pathology. Our study supports the use of behavioral markers as early indicators of ongoing AD pathology during the preclinical phase.

SUBMITTER: Samaey C

PROVIDER: S-EPMC6908963 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Early Cognitive and Behavioral Deficits in Mouse Models for Tauopathy and Alzheimer's Disease.

Samaey Celine C Schreurs An A Stroobants Stijn S Balschun Detlef D

Frontiers in aging neuroscience 20191206

Neurocognitive disorders, among which Alzheimer's disease (AD), have become one of the major causes of death in developed countries. No effective disease-modifying therapy is available, possibly because current treatments are administered too late to still be able to intervene in the disease progress. AD is characterized by a gradual onset with subclinical neurobiological and behavioral changes that precede diagnosis with years to even decades. The earlier the diagnosis, the earlier potential tr ...[more]

PMID: 31866856

Similar Datasets

Project description:Clinical and neuropathological studies have shown that tau pathology better correlates with the severity of dementia than amyloid plaque burden, making tau an attractive target for the cure of Alzheimer's disease. We have explored whether passive immunization with the 12A12 monoclonal antibody (26-36aa of tau protein) could improve the Alzheimer's disease phenotype of two well-established mouse models, Tg2576 and 3xTg mice. 12A12 is a cleavage-specific monoclonal antibody which selectively binds the pathologically relevant neurotoxic NH226-230 fragment (i.e. NH2htau) of tau protein without cross-reacting with its full-length physiological form(s). We found out that intravenous administration of 12A12 monoclonal antibody into symptomatic (6 months old) animals: (i) reaches the hippocampus in its biologically active (antigen-binding competent) form and successfully neutralizes its target; (ii) reduces both pathological tau and amyloid precursor protein/amyloidβ metabolisms involved in early disease-associated synaptic deterioration; (iii) improves episodic-like type of learning/memory skills in hippocampal-based novel object recognition and object place recognition behavioural tasks; (iv) restores the specific up-regulation of the activity-regulated cytoskeleton-associated protein involved in consolidation of experience-dependent synaptic plasticity; (v) relieves the loss of dendritic spine connectivity in pyramidal hippocampal CA1 neurons; (vi) rescues the Alzheimer's disease-related electrophysiological deficits in hippocampal long-term potentiation at the CA3-CA1 synapses; and (vii) mitigates the neuroinflammatory response (reactive gliosis). These findings indicate that the 20-22 kDa NH2-terminal tau fragment is crucial target for Alzheimer's disease therapy and prospect immunotherapy with 12A12 monoclonal antibody as safe (normal tau-preserving), beneficial approach in contrasting the early Amyloidβ-dependent and independent neuropathological and cognitive alterations in affected subjects.

Dataset Information

Early Cognitive and Behavioral Deficits in Mouse Models for Tauopathy and Alzheimer's Disease.

Publications

Early Cognitive and Behavioral Deficits in Mouse Models for Tauopathy and Alzheimer's Disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets