Alzheimer disease (AD) is featured by deposition of
beta-amyloid peptides, phosphorylated
tau protein (3- and 4-repeat tau) and frequent
alpha-synuclein (aSyn) deposits. Lewy body diseases (LBD), such as sporadic
Parkinson disease (PD) and
dementia with Lewy bodies (DLB), show aSyn-positive deposits in neurons, neurites, glia, and presynaptic terminals, while
frontotemporal dementias present tau-positive and tau-negative,
ubiquitin- and TDP-43-positive neuronal and glial inclusions. The latter have also been observed in AD, PD, PD
dementia and motor neuron disorders. Molecular interactions between major
proteins, which may occur within the same brain in various distribution patterns, cause variable phenotypes and mixed pathologies, e.g. AD with aSyn pathology in the brainstem and amygdala, PD and DLB with AD lesions, and
frontotemporal dementia with a mixture of various deposits, while others are featured by one principal pathology without other lesions (e.g. tangle-predominant type of
dementia, pure PD, brainstem-predominant LBD).
CONCLUSION: Animal models and in vitro studies showing co-occurrence and mutual promotion of fibrillation of these
proteins indicate their synergistic interactions in the pathogenesis of these disorders which, at least in part, are genetically influenced.