Objective: Objective: The aim of this paper is to present the result of the whole body screening of Lewy body pathology by Brain Bank for Aging Research (BBAR) and its contribution to “Brain First” vs “Body First” hypothesis of Parkinson’s disease.

Background: Brain Bank for Aging Research belongs to Tokyo Metropolitan Institute for Geriatrics and Gerontology, whose aim is to support elderly population living in Tokyo suburban area.  The first kin of relatives” informed consent is the legal base and full autopsy is a rule. We started the project in 1972 and accumulated more than two thousand cases.

Method: Full autopsy was done in all cases registered to BBAR. We immunochistochemically screened the cases with antibodies raised aganst phosphorylated alphas synuclein (pSyn#64), phosphorylated tau (AT8), four repeat tau (RD4), three repeat tau (RD3), amyloid beta (12B2), TDP43 (pSer409/410) and ubiquitin (Sigma) of selected anatomical sites of the central nervous system.  In addition, the peripheral nervous sytstem, including skin, adrenal gland, thoracic sympathetic ganglia, esophgogastric junction and submindibular galnd was immunohistochemically screened with pSyn#64.

Results: One third of our aged population with average age of 82.5 years contained Lewy body pathology in the central and peripheral nervous systems.  The ealiest deposition site of alpha- synuclein in our cohort was either an olfactory bulb or thoracic sympathetic ganglia. In later stage, the deposition propagated to both the peripheral and central nervous systems. The body deposition strongly correlated with that of the brain stem and the deposition of olfactory bulb strongly correlsted with that of amygdala. One consulted case of PD with olfactory hypoplasia showed deposition of alpha synuclein in the peripheral nervous system, brain stem and very weakly limibic systems.   Two autopsy cases of pure autonomic failure showed similar deposition of alpha synuclein, relatively sparing substantia nigra.

Conclusion: Our results supported “BodyFirst” vs “Brain First” hypothesis of alpha- synuclein. Further accumulation of full autopsy cases with immunohistochemical screenintg of anti- phosphorylated alpha- synuclein antibody may provide propagation mechanisim of alpha- synuclein resulting in Parkinson disease.

References: Tanei Z, Saito, Y, Ito S, Matsubara T, Motoda A, Yamazaki M, Sakashita, Y, Kawakami I, Ikemura M, Tanaka S, Sengoku R, Arai T, Murayama S: Lewy pathology of the esophagus correlates with the progression of Lewy body disease: a Japanese cohort study of autopsy cases. Acta Neuropath 2021; 141:25-37.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-contribution-of-brain-bank-for-aging-research-to-pathomechanism-of-parkinsons-disease/