Beyond amyloid plaque, targeting α-synuclein in Alzheimer disease: The battle continues

Alzheimer's disease (AD) is the most common neurodegenerative brain disease and represents the most frequent type of dementia characterized by cognitive impairment and amnesia. AD neuropathology is connected to the development of synaptic dysfunction and loss of synaptic homeostasis due to an imbalance in the production and clearance of β-amyloid (Aβ) and intracellular neurofibrillary tangles (NFTs). However, AD neuropathology is complex and may relate to the deposition of other misfolded proteins, such as alpha-synuclein (α-Syn). Of note, α-Syn, which is involved in the pathogenesis of Parkinson disease (PD) and Lewy body (LB) dementia, is also implicated in AD neuropathology. However, the potential role of α-Syn in AD neuropathology is elusive. Therefore, this review aims to discuss the pathological role of α-Syn in AD and how targeting α-Syn aggregates may be effective in treating AD.