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Review
. 2015 Dec 2:9:464.
doi: 10.3389/fncel.2015.00464. eCollection 2015.

Tau Oligomers: The Toxic Player at Synapses in Alzheimer's Disease

Marcos J Guerrero-Muñoz  1 , Julia Gerson  1 , Diana L Castillo-Carranza  1
Affiliations
Review

Tau Oligomers: The Toxic Player at Synapses in Alzheimer's Disease

Marcos J Guerrero-Muñoz et al. Front Cell Neurosci. .

Abstract

Alzheimer's disease (AD) is a progressive disorder in which the most noticeable symptoms are cognitive impairment and memory loss. However, the precise mechanism by which those symptoms develop remains unknown. Of note, neuronal loss occurs at sites where synaptic dysfunction is observed earlier, suggesting that altered synaptic connections precede neuronal loss. The abnormal accumulation of amyloid-β (Aβ) and tau protein is the main histopathological feature of the disease. Several lines of evidence suggest that the small oligomeric forms of Aβ and tau may act synergistically to promote synaptic dysfunction in AD. Remarkably, tau pathology correlates better with the progression of the disease than Aβ. Recently, a growing number of studies have begun to suggest that missorting of tau protein from the axon to the dendrites is required to mediate the detrimental effects of Aβ. In this review we discuss the novel findings regarding the potential mechanisms by which tau oligomers contribute to synaptic dysfunction in AD.

Keywords: Alzheimer’s disease; Aβ oligomers; dendrites; synapsis; tau oligomers.

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Figures

FIGURE 1
FIGURE 1
Schematic illustrating the pathological role of tau at dendritic spines. ß-amyloid (Aβ) oligomers directly or indirectly lead to the dystrophic changes in neurites mediated by tau. Hyperphosphorylated tau targets the kinase, Fyn, to the postsynaptic compartment. Fyn phosphorylates NR2B, a subunit of the N-methyl-D-aspartate receptor (NMDAR), resulting in the over-activation of NMDAR, followed by increased concentration of Ca2+ in the cytoplasmic compartment. Aβ oligomers (Aβo) seed tau misfolding and aggregation by direct interaction resulting in tau oligomer formation at dendritic spines. All of these pathways converge in the aggregation of tau protein, spine loss, and consequently, cognitive impairment.
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