Acetylated tau in Alzheimer's disease: An instigator of synaptic dysfunction underlying memory loss: Increased levels of acetylated tau blocks the postsynaptic signaling required for plasticity and promotes memory deficits associated with tauopathy

• Published in: BioEssays Vol. 39; no. 4
• Main Authors: Tracy, Tara E, Gan, Li
• Format: Journal Article
• Language: English
• Published: United States 01-04-2017
• Subjects: Acetylation; Alzheimer Disease - metabolism; Alzheimer Disease - physiopathology; Animals; Brain - metabolism; Brain - physiopathology; Disease Models, Animal; Humans; Memory Disorders - metabolism; Protein Processing, Post-Translational; Synapses - metabolism; tau Proteins - metabolism; Tauopathies - metabolism; Tauopathies - physiopathology; KIBRA; acetylation; tau; synaptic plasticity; Alzheimer's disease; long-term potentiation
• ISSN: 0265-9247; 1521-1878
• DOI: 10.1002/bies.201600224

Pathogenesis in tauopathies involves the accumulation of tau in the brain and progressive synapse loss accompanied by cognitive decline. Pathological tau is found at synapses, and it promotes synaptic dysfunction and memory deficits. The specific role of toxic tau in disrupting the molecular networks that regulate synaptic strength has been elusive. A novel mechanistic link between tau toxicity and synaptic plasticity involves the acetylation of two lysines on tau, K274, and K281, which are associated with dementia in Alzheimer's disease (AD). We propose that an increase in tau acetylated on these lysines blocks the expression of long-term potentiation at hippocampal synapses leading to impaired memory in AD. Acetylated tau could inhibit the activity-dependent recruitment of postsynaptic AMPA-type glutamate receptors required for plasticity by interfering with the postsynaptic localization of KIBRA, a memory-associated protein. Strategies that reduce the acetylation of tau may lead to effective treatments for cognitive decline in AD.