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Neuropathological correlates of parkinsonian disorders in a large Dutch autopsy series

Onderzoeksgroep Huitinga
Publicatiejaar 2020
Gepubliceerd in Acta neuropathologica communications
Auteur(s) H. Geut, Dagmar H Hepp, E.M.J. Foncke, Henk W Berendse, Annemieke J M Rozemuller, I. Huitinga, Wilma D J van de Berg

The clinical diagnosis in patients with parkinsonian disorders can be challenging, and a definite diagnosis requires neuropathological confirmation. The aim of this study was to examine whether a clinical diagnosis of Parkinson’s disease (PD) and atypical parkinsonian disorders predict the presence of Lewy pathology (LP) and concomitant neuropathological lesions.We included 293 donors with a history of parkinsonism without dementia at disease onset, collected by the Netherlands Brain Bank (NBB) from 1989 to 2015. We retrospectively categorized donors according the International Parkinson and Movement Disorder Society clinical diagnostic criteria for PD (MDS-PD criteria) as ‘not PD’, ‘probable PD’ or ‘established PD’. We compared the final clinical diagnosis to presence of neuropathological lesions as defined by BrainNet Europe and National Institute on Aging – Alzheimer’s Association guidelines.LP was present in 150 out of 176 donors (85%) with a clinical diagnosis of PD, in 8 out of 101 donors (8%) with atypical parkinsonian disorders and in 4 out of 16 donors (25%) without a definite clinical diagnosis. Independent from age at death, stages of amyloid-β, but not neurofibrillary tau or neuritic plaques, were higher in donors with LP compared to other types of pathology (p = 0.009). The MDS-PD criteria at a certainty level of ‘probable PD’ predicted presence of LP with a diagnostic accuracy of 89.3%. Among donors with LP, ‘established PD’ donors showed similar Braak α-synuclein stages and stages of amyloid-β, neurofibrillary tau and neuritic plaques compared to ‘not PD’ or ‘probable PD’ donors.In conclusion, both a clinical diagnosis of PD as well as MDS-PD criteria accurately predicted presence of LP in NBB donors. LP was associated with more widespread amyloid-β pathology, suggesting a link between amyloid-β accumulation and LP formation.

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