Lewy body/alpha-synucleinopathy in schizophrenia and depression: a preliminary neuropathological study

The role of alpha-synuclein (alphaSyn) in schizophrenia is unknown, whereas in a recent animal model of depression, alpha- and gamma-synuclein have been related to its pathophysiology. Previous biochemical studies in Brodmann area 9 showed significant reduction of alphaSyn in both chronic schizophrenia and bipolar disorder. Here, prevalence and cerebral distribution of alphaSyn were examined in 80 autopsy cases of elderly subjects (41 chronic schizophrenia, 12 late live depression/LLD and bipolar disorder/BD, and 27 age-matched controls without neuropsychiatric disorders). Using immunohistochemistry, alphaSyn-positive lesions (Lewy bodies and neurites) were assessed semiquantitatively. Among 41 chronic schizophrenics, all except one showing low neuritic Braak stages (mean 1.46), three brains (7.3%) revealed only few alphaSyn-positive inclusions restricted to medullary nuclei. Among 12 LLD and BD patients with mean Braak stage 2.25, alphaSyn-positive pathology was seen in two cases (16.7%) with clinical LLD, but none in BD. Among 27 controls, showing mean neuritic Braak stage 2.6, seven brains (26%) with higher mean age showed alphaSyn-positive lesions, either isolated in substantia nigra and nucleus basalis of Meynert (n = 2 each), in medullary nuclei, locus ceruleus and substantia nigra (n = 2), with additional involvement of nucleus basalis (n = 1). This first preliminary study in non-demented psychiatric disorders indicates that alphaSyn/Lewy pathology in chronic schizophrenia is significantly less frequent than in clinically healthy elderly people (P < 0.01), showing 10-30% of so-called incidental Lewy body disease. Among chronic affective disorders, according to our small cohort, the incidence of Lewy-pathology in LLD appears to be comparable to a healthy elderly population, whereas its occurence in BD is to be elucidated.