The main pathological characteristic of PD is cell death in the substantia nigra and more specifically the ventral part of the pars compacta, affecting up to 70% of the cells by the time the patient dies. The mechanisms by which the brain cells are lost are varied. One mechanism consists of an abnormal accumulation of the protein alpha-synuclein bound to ubiquitin in the damaged cells. This protein accumulation forms inclusions called Lewy bodies.
According to the Braak staging Lewy bodies first appear in the olfactory bulb, medulla oblongata and pontine tegmentum, individuals at this stage being asymptomatic. As the disease evolves, Lewy bodies later attain the substantia nigra, areas of the midbrain and basal forebrain, and finally reach areas of the neocortex.
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