Abstract Details

Title a-synuclein propagation via olfactory pathway induces olfactory bulb atrophy and widespread glucose hypometabolism in a non-human primate model.

Topic Movement Disorders

Presentation(s) P1 - Poster Session 1 (9:00 AM-5:00 PM)

Poster/Presentation
Number 268

Objective

We investigated how α-synuclein (α-Syn) pathology spreads from the olfactory bulb (OB) and how the pathology affects brain structure and activity in non-human primates (NHPs).

Background Lewy body diseases (LBDs) are neurodegenerative diseases characterized by α-Syn aggregates, called Lewy body, which encompass Parkinson’s disease or dementia with Lewy bodies. In LBDs, α-Syn aggregates are believed to propagate in the brain like prion via two major pathways: the olfactory and vagal nerve pathways. It has been also shown that inoculation of α-Syn preformed fibrils (PFFs) into the mouse OB induced propagation of α-Syn pathology mainly along the olfactory pathway and the limbic system, however it remains unclear how applicable these results are to human LBDs, because of the considerable differences in the brain structure and olfactory system between rodents and primates. To the best of our knowledge, this is the first study describing the propagation of α-Syn pathology via olfactory pathway in NHPs.

Design/Methods We inoculated α-Syn PFFs into the unilateral OB of four common marmosets, and performed pathological analyses, manganese-enhanced MRI (MEMRI), and ¹⁸F-fluoro-2-deoxy-D-glucose positron emission tomography (¹⁸F-FDG-PET) at 3 or 6 months postinoculation.

Results Severe α-Syn pathology was observed within the olfactory pathway and limbic system, while mild α-Syn pathology was seen in a wide range of brain regions, including the substantia nigra pars compacta, locus coeruleus, and even dorsal motor nucleus of the vagus nerve. The brain imaging analyses revealed reduction in volume of the OB and glucose hypometabolism in widespread brain regions, including the occipital lobe, which extended beyond the pathologically affected regions.

Conclusions We generated a novel non-human primate LBD model with α-Syn propagation from the OB. This model suggests that α-Syn propagation from the OB is related to olfactory and cognitive dysfunction in LBDs.

Authors/Disclosures
Masanori Sawamura, MD (Kyoto University Hospital) PRESENTER	Dr. Sawamura has nothing to disclose.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Ryosuke Takahashi, MD (Kyoto University Graduate School of Medicine)	Dr. Takahashi has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Kan Institute. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda Pharma. Dr. Takahashi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Ono Pharma. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Kyowa Kirin Pharma. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Otsuka Pharma. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Abbvie. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Chugai Pharma. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Argenix. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alnyrum. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sumitomo Pharma. The institution of Dr. Takahashi has received research support from MEXT. Japan. The institution of Dr. Takahashi has received research support from AMED, Japan. The institution of Dr. Takahashi has received research support from JST, Japan. The institution of Dr. Takahashi has received research support from MHLW, Japan. The institution of Dr. Takahashi has received research support from Sumitomo Pharma. The institution of Dr. Takahashi has received research support from Takeda Pharma. The institution of Dr. Takahashi has received research support from Otsuka Pharma. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving as a PO with AMED, Japan. Dr. Takahashi has received personal compensation in the range of $500-$4,999 for serving as a PO with JST, Japan.

��ɫ��

��ɫ��