Patterns of a-synuclein are altered in patients with multiple dementias

Dementia patients with combinations of Alzheimer’s disease (AD), Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) show significantly different distribution of the protein alpha-synuclein than they would with one diagnosis, according to a presentation during last week’s annual meeting of the American Academy of Neurology (AAN).

Jon B. Toledo, MD, a researcher at the University of Pennsylvania in Philadelphia, and colleagues endeavored to track the different patterns of alpha-synuclein pathology in dementia patients to see how it changed in patients with different combinations of neurodegenerative disease.

For this study, the researchers looked at the distribution of a-synuclein in 313 DLB patients with Alzheimer’s and did a comparison study with the pattern of a-synuclein in 134 patients with PD with no sign of Alzheimer’s and another 71 Parkinson’s patients with Alzheimer’s.

"[AD and PD] are the two most common, frequently co-ocurring, neurodegenerative diseases,” wrote Toledo et al. “[DLB] is defined by dementia with fluctuating cognitive symptoms and the appearance of a Parkinsonian syndrome more than one year after dementia onset. Staging systems have been proposed for tau and amyloid deposits in AD as well as for alpha-synuclein pathology (ASP) in PD and DLB although no consensus has been reached.”

Results of the study showed ASP predominately in the amygdala in patients with AD and DLB, but not PD.

Patients with DLB showed lower burden of brainstem, subcortical and frontal a-synuclein. Those with DLB only had less a-synuclein burden in the substantia nigra than patients with PD or a combination of PD and AD.

Patients with PD had less a-synuclein pathology in the temporal and angular cortex than those with both PD and AD or DLB alone.

This new data informs clinicians about the very real impact that concomitant neurodegenerative disease has on typical distribution patterns of neuropathology.