Objective: To analyze the frequency and severity of co-pathologies in PSP patients and their relevance for the clinical presentation and progression in PSP.

Background: The phenotypic presentation of neurodegenerative disorders (NDD), including PSP, is largely driven by the specific protein aggregations and their regional distribution within the brain.  However, given that NDD typically manifest later in life, it is not surprising that additional proteinopathies and vascular co-pathology may co-exist and may also contribute to complex clinical presentations.

Method: We analyzed clinical and neuropathological features of 101 patients with pathologically confirmed diagnosis of PSP. Neuropathological diagnoses and stages of co-pathologies were established according to valid criteria, including Alzheimer’s disease, argyrophilic grains, Lewy-related pathology, transactive response DNA-binding protein 43 (TDP-43) pathology, fused in sarcoma (FUS) pathology, cerebral amyloid angiopathy and small vessel disease. Demographic data and major clinical disease milestones of PSP (frequency and latency to onset) were extracted from patient’s files.

Results: Only 8% of 101 patients presented with pure PSP pathology in absence of any co-pathologies. Alzheimer’s disease-related pathology was the most frequent co-pathology (84%), followed by argyrophilic grains (58%), both occurring as single co-pathology or in combination with other proteinopathies or cerebrovascular disease. Lewy-related and TDP-43 co-pathology occurred rarely (8% and 6%, respectively). FUS-positive cases were not found. While being common, co-pathology in PSP was mostly mild in severity, with the exception of frequently widespread argyrophilic grains. Small vessel disease was also frequent (65%), while cerebral amyloid angiopathy (25%) occurred only in the presence of Alzheimer’s disease-related changes. No significant differences were found between any of the co-pathology subgroups in terms of demographic data and disease milestones.

Conclusion: In PSP, concomitant neurodegenerative proteinopathies or cerebrovascular disease is very frequent, but generally mild in severity, and without striking affect on the clinical presentation. This finding underscores that the severity and distribution of tau pathology is the principle driver of clinical symptoms in PSP, which is relevant information for the development of disease-modifying therapies.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/concomitant-brain-pathologies-have-no-major-impact-on-clinical-milestones-in-progressive-supranuclear-palsy/