Understanding the effect of oAβ and oTau proteins on impaired LTP within Alzheimer’s Disease

Alzheimer’s Disease (AD) is associated with decreased memory recall, where synaptic plasticity is impaired between neurons. Synaptic plasticity is the ability to modify the strength or efficacy of synaptic transmission at synapses between neurons. One of the main forms of impaired synaptic plasticity includes long-term potentiation (LTP). Studies have shown that one of the main causes of the inhibiting LTP is through oligomeric amyloid-beta (oAβ) and oligomeric tau (oTau) proteins. oAβ was shown to impair glutamatergic synaptic transmission and subunit receptors including extrasynaptic NMDAR and NR2B respectively. Hippocampal slices were used and treated with CHO/7PA2 cells containing a V717F hAPP751 AD mutation. oAβ was found to inhibit the extrasynaptic NMDARs along with the NR2B antagonists and produce impaired LTP. Using the extrasynaptic NMDARs was shown to dephosphorylate CREB, impairing LTP, not only in oAβ but also in oTau. Additionally, oTau was shown to impair LTP through protein kinases GSK-3B and dephosphorylate tau through protein phosphatase PP2A, and oTau was able to impair LTP through tau isoform 4R/2N. Understanding the effect of oligomeric forms of protein aggregation within AD can help advance treatment development and use protein aggregation as a treatment.