Synaptic Disruption by Soluble Oligomers in Patients with Alzheimer’s and Parkinson’s Disease

Berenice A. Gutierrez, Agenor Limon

Research output: Contribution to journalReview articlepeer-review

Abstract

Neurodegenerative diseases are the result of progressive dysfunction of the neuronal activity and subsequent neuronal death. Currently, the most prevalent neurodegenerative diseases are by far Alzheimer’s (AD) and Parkinson’s (PD) disease, affecting millions of people worldwide. Although amyloid plaques and neurofibrillary tangles are the neuropathological hallmarks for AD and Lewy bodies (LB) are the hallmark for PD, current evidence strongly suggests that oligomers seeding the neuropathological hallmarks are more toxic and disease-relevant in both pathologies. The presence of small soluble oligomers is the common bond between AD and PD: amyloid β oligomers (AβOs) and Tau oligomers (TauOs) in AD and α-synuclein oligomers (αSynOs) in PD. Such oligomers appear to be particularly increased during the early pathological stages, targeting synapses at vulnerable brain regions leading to synaptic plasticity disruption, synapse loss, inflammation, excitation to inhibition imbalance and cognitive impairment. Absence of TauOs at synapses in individuals with strong AD disease pathology but preserved cognition suggests that mechanisms of resilience may be dependent on the interactions between soluble oligomers and their synaptic targets. In this review, we will discuss the current knowledge about the interactions between soluble oligomers and synaptic dysfunction in patients diagnosed with AD and PD, how it affects excitatory and inhibitory synaptic transmission, and the potential mechanisms of synaptic resilience in humans.

Original languageEnglish (US)
Article number1743
JournalBiomedicines
Volume10
Issue number7
DOIs
StatePublished - Jul 2022

Keywords

  • E/I balance
  • neurodegenerative diseases
  • oligomers

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)

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