The presence of protein aggregates is a hallmark of many neurodegenerative
diseases, including Parkinson’s disease (PD), Alzheimer’s disease (AD), and
frontotemporal lobar degeneration (FTLD). Traditionally, each disease has been
associated with the aggregation of specific proteins, which serve as
disease-specific biomarkers. For example, aggregates of -synuclein
(-syn) are found in -synucleinopathies such as PD, dementia
with Lewy bodies (DLB), and multiple system atrophy (MSA). Similarly, AD is
characterized by aggregates of amyloid-beta (A) and tau proteins.
However, it has been observed that these protein aggregates can also occur in
other neurodegenerative diseases, contributing to disease progression. For
instance, -syn aggregates have been detected in AD, Down syndrome,
Huntington’s disease, prion diseases, and various forms of FTLD. Similarly,
A aggregates have been found in conditions like DLB and PD. Tau
aggregates, in addition to being present in primary tauopathies, have been
identified in prion diseases, -synucleinopathies, and cognitively
healthy aged subjects. Finally, aggregates of TDP-43, typically associated with
FTLD and amyotrophic lateral sclerosis (ALS), have been observed in AD,
progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), MSA, DLB,
and other neurodegenerative diseases. These findings highlight the complexity of
protein aggregation in neurodegeneration and suggest potential interactions and
common mechanisms underlying different diseases. A deeper understating of this
complex scenario may eventually lead to the identification of a better
elucidation of the pathogenetic mechanisms of these devastating conditions and
hopefully new therapeutic stragegies.