Mechanisms of Neurodegeneration Interact to Contribute to Multiple Conditions

The common neurodegenerative conditions are characterized by the aggregation of a few types of misfolded or otherwise altered proteins, harmful to cell and tissue function. Each form of protein aggregate is not a process occurring in isolation; their presence and their consequences interact with one another. Neurodegeneration is a holistic process, and the scientific and medical communities carve pieces out of that whole and call them diseases or disease mechanisms. It doesn't do to lose sight of the fact that these neatly boxed classifications are to some degree arbitrary lines in the sand.

Many people with Lewy body diseases (LBDs) such as Parkinson's disease (PD) ultimately develop dementia, and many have amyloid-β (Aβ) plaques and tau tangles. Do they have two diseases at the same time, or is this combination of scourges a unique entity unto itself? Researchers reported that people with PD who carry genetic risk variants for Alzheimer's disease (AD) were more likely to become cognitively impaired. Similarly, AD variants predicted which PD patients harbored Aβ and tau proteopathies in their brains. In people with dementia with Lewy bodies (DLB), Aβ plaques seemed to worsen cognitive decline more than tau tangles did, suggesting an etiology distinct from AD. Although the interactions between α-synuclein, Aβ, and tau still need more clarification, some suggested that therapies targeting Aβ might benefit people with Lewy body diseases.

Studies suggest that Aβ could exacerbate both tau and α-synuclein aggregation in LBD. This may be why Aβ-targeted therapies could benefit people with synucleinopathies. However, anti-Aβ therapies have failed to benefit cognition in people with AD, so why would they work for LBD? In LBDs, Aβ appears to exacerbate both tau tangles and α-synuclein aggregation, either of which could lead to dementia. Targeting Aβ might dismantle this toxic triplet. Second, while Aβ plays the role of instigator in AD, it appears to drive progression throughout the disease process in LBD. Therefore, while ridding the brain of Aβ may be too little, too late, for people with symptomatic AD, it could slow the disease in people with LBD.

Link: https://www.alzforum.org/news/community-news/av-lewy-body-disease-two-diseases-once-or-another-beast-entirely

Comments

Post a comment; thoughtful, considered opinions are valued. New comments can be edited for a few minutes following submission. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.