Dataset Information

A soluble truncated tau species related to cognitive dysfunction is elevated in the brain of cognitively impaired human individuals.

ABSTRACT: Neurofibrillary tangles are a pathological hallmark of Alzheimer's disease, and their levels correlate with the severity of cognitive dysfunction in humans. However, experimental evidence suggests that soluble tau species cause cognitive deficits and memory impairment. Our recent study suggests that caspase-2 (Casp2)-catalyzed tau cleavage at aspartate 314 mediates synaptic dysfunction and memory impairment in mouse and cellular models of neurodegenerative disorders. ?tau314, the C-terminally-truncated cleavage products, are soluble and present in human brain. In addition, levels of ?tau314 proteins are elevated in the brain of the cognitively impaired individuals compared to the cognitively normal individuals, indicating a possible role for ?tau314 proteins in cognitive deterioration. Here we show that (1) ?tau314 proteins are present in the inferior temporal gyrus of human brains; (2) ?tau314 proteins are generated from all six tau splicing isoforms, (3) levels of both Casp2 and ?tau314 proteins are elevated in cognitively impaired individuals compared to cognitively normal individuals, and (4) levels of ?tau314 proteins show a modest predictive value for dementia. These findings advance our understanding of the characteristics of ?tau314 proteins and their relevance to cognitive dysfunction and shed light on the contribution of Casp2-mediated ?tau314 production to cognitive deterioration.

SUBMITTER: Liu P

PROVIDER: S-EPMC7052165 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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A soluble truncated tau species related to cognitive dysfunction is elevated in the brain of cognitively impaired human individuals.

Liu Peng P Smith Benjamin R BR Montonye Michelle L ML Kemper Lisa J LJ Leinonen-Wright Kailee K Nelson Kathryn M KM Higgins LeeAnn L Guerrero Candace R CR Markowski Todd W TW Zhao Xiaohui X Petersen Ashley J AJ Knopman David S DS Petersen Ronald C RC Ashe Karen H KH

Scientific reports 20200302 1

Neurofibrillary tangles are a pathological hallmark of Alzheimer's disease, and their levels correlate with the severity of cognitive dysfunction in humans. However, experimental evidence suggests that soluble tau species cause cognitive deficits and memory impairment. Our recent study suggests that caspase-2 (Casp2)-catalyzed tau cleavage at aspartate 314 mediates synaptic dysfunction and memory impairment in mouse and cellular models of neurodegenerative disorders. Δtau314, the C-terminally-tr ...[more]

PMID: 32123248

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Dataset Information

A soluble truncated tau species related to cognitive dysfunction is elevated in the brain of cognitively impaired human individuals.

Publications

A soluble truncated tau species related to cognitive dysfunction is elevated in the brain of cognitively impaired human individuals.

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