Cognitive dysfunction in animal models of human lewy-body dementia

Front Aging Neurosci. 2024 Jul 22:16:1369733. doi: 10.3389/fnagi.2024.1369733. eCollection 2024.

Abstract

Cognitive impairments are a common feature of synucleinopathies such as Parkinson's Disease Dementia and Dementia with Lewy Bodies. These pathologies are characterized by accumulation of Lewy bodies and Lewy neurites as well as neuronal cell death. Alpha-synuclein is the main proteinaceous component of Lewy bodies and Lewy neurites. To model these pathologies in vivo, toxins that selectively target certain neuronal populations or different means of inducing alpha-synuclein aggregation can be used. Alpha-synuclein accumulation can be induced by genetic manipulation, viral vector overexpression or the use of preformed fibrils of alpha-synuclein. In this review, we summarize the cognitive impairments associated with different models of synucleinopathies and relevance to observations in human diseases.

Keywords: Parkinson’s disease; Parkinson’s disease dementia; animal models; dementia with lewy bodies; lewy body dementia; preformed fibril.

Publication types

  • Review

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. The study was funded by the joint efforts of The Michael J. Fox Foundation for Parkinson’s Research (MJFF) and the Aligning Science Across Parkinson’s (ASAP) initiative. MJFF administers the grant ASAP-020608 on behalf of ASAP and itself. MK was also supported by funding from the JPB Foundation for Medical Research.