Co-aggregation of amyloidogenic proteins in age-related neurodegenerative diseases.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing preclinical, mechanistic, and clinical literature without systematic review or meta-analysis methodology
PubMed 42031321 · doi:10.1016/j.arr.2026.103148
What was done
The authors conducted a narrative synthesis integrating biophysical, cellular, animal, and human studies on the heterotypic co-aggregation of key amyloidogenic proteins, including Tau, alpha-synuclein (alpha-syn), amyloid-beta (Abeta), and TAR DNA-binding protein 43 (TDP-43). Based on this literature, they proposed a conceptual network framework examining how age-related alterations in lipid membranes, redox balance, proteostasis, and genetic factors drive mixed proteinopathies, and evaluated translational implications for biomarkers and multi-targeted therapeutics.
What was found
The abstract provides a qualitative conceptual framework rather than quantitative experimental results or pooled effect estimates; no numerical data are reported. The synthesis reports that amyloidogenic proteins cross-seed, co-localize, and mutually modulate aggregation kinetics and cellular toxicity in mixed dementias and overlapping neurodegenerative disorders, arguing against a one-protein-one-disease model.
Why it matters
This paper reframes age-related neurodegeneration as an interconnected network of co-aggregating proteins, highlighting the need for multi-analyte fluid biomarkers and multi-targeted therapies capable of addressing concurrent proteinopathies.
Limits
The paper is a narrative review with no primary empirical data, systematic search protocol, quantitative meta-analysis, or formal risk-of-bias evaluation. The abstract reports no sample sizes, effect sizes, or quantitative metrics.
Cited by
- supports Virtually all neurodegenerative diseases feature the aggregation of abnormal protein clumps either inside neurons or in the extracellular spaces between neurons.