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Relationship of phosphorylated alpha-synuclein and tau accumulation to Abeta deposition in the cerebral cortex of dementia with Lewy bodies.
Exp Neurol. 2008 Apr; 210(2):409-20.EN

Abstract

Alpha-synuclein accumulated in the brain of dementia with Lewy bodies (DLB) is phosphorylated at serine129 (palpha-synuclein). We investigated the accumulation of palpha-synuclein in the brains of patients with DLB and Alzheimer's disease (AD). We employed 18 DLB patients with neocortical Lewy body type pathology (nLBTP) with or without AD. We also employed the same number of AD cases without significant nLBTP. We refer to the former group as the nLBTP group and to the latter as the AD type pathology (ADTP) group. In the nLBTP group, palpha-synuclein positive neurite pathology such as threads and dots occurs in all layers of the temporal neocortex. It was comparable in degree with tau pathology in AD. Fifteen cases in the nLBTP group were associated with Abeta deposition that meets the CERAD plaque score "C" and one case with a score "B". In these plaque-associated cases, the severity of palpha-synuclein pathology was related to the degree of Abeta deposition. In the cases with relatively moderate Abeta deposition, tau pathology was disproportionately mild in the nLBTP group, while the total of tau and palpha-synuclein pathology was proportionate to Abeta deposition in both the nLBTP and ADTP groups. Our results support the ideas that there is an overlap in the pathology between AD and DLB and that Abeta promotes accumulation of both alpha-synuclein and tau. The procession from Abeta to neurite pathology in the cerebral cortex of AD and DLB may be unifiable.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Obi K
Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
Akiyama H
No affiliation info available
Kondo H
No affiliation info available
Shimomura Y
No affiliation info available
Hasegawa M
No affiliation info available
Iwatsubo T
No affiliation info available
Mizuno Y
No affiliation info available
Mochizuki H
No affiliation info available

MeSH

AgedAged, 80 and overAmyloid beta-PeptidesAnalysis of VarianceCerebral CortexFemaleHumansLewy BodiesLewy Body DiseaseMaleMicroscopy, ImmunoelectronMiddle AgedPhosphorylationPlaque, AmyloidSerineStatistics, Nonparametricalpha-Synucleintau Proteins

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18164295

Citation

Obi, Kimiko, et al. "Relationship of Phosphorylated Alpha-synuclein and Tau Accumulation to Abeta Deposition in the Cerebral Cortex of Dementia With Lewy Bodies." Experimental Neurology, vol. 210, no. 2, 2008, pp. 409-20.
Obi K, Akiyama H, Kondo H, et al. Relationship of phosphorylated alpha-synuclein and tau accumulation to Abeta deposition in the cerebral cortex of dementia with Lewy bodies. Exp Neurol. 2008;210(2):409-20.
Obi, K., Akiyama, H., Kondo, H., Shimomura, Y., Hasegawa, M., Iwatsubo, T., Mizuno, Y., & Mochizuki, H. (2008). Relationship of phosphorylated alpha-synuclein and tau accumulation to Abeta deposition in the cerebral cortex of dementia with Lewy bodies. Experimental Neurology, 210(2), 409-20. https://doi.org/10.1016/j.expneurol.2007.11.019
Obi K, et al. Relationship of Phosphorylated Alpha-synuclein and Tau Accumulation to Abeta Deposition in the Cerebral Cortex of Dementia With Lewy Bodies. Exp Neurol. 2008;210(2):409-20. PubMed PMID: 18164295.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Relationship of phosphorylated alpha-synuclein and tau accumulation to Abeta deposition in the cerebral cortex of dementia with Lewy bodies. AU - Obi,Kimiko, AU - Akiyama,Haruhiko, AU - Kondo,Hiromi, AU - Shimomura,Yoko, AU - Hasegawa,Masato, AU - Iwatsubo,Takeshi, AU - Mizuno,Yoshikuni, AU - Mochizuki,Hideki, Y1 - 2007/12/03/ PY - 2007/07/31/received PY - 2007/11/11/revised PY - 2007/11/15/accepted PY - 2008/1/1/pubmed PY - 2008/6/21/medline PY - 2008/1/1/entrez SP - 409 EP - 20 JF - Experimental neurology JO - Exp Neurol VL - 210 IS - 2 N2 - Alpha-synuclein accumulated in the brain of dementia with Lewy bodies (DLB) is phosphorylated at serine129 (palpha-synuclein). We investigated the accumulation of palpha-synuclein in the brains of patients with DLB and Alzheimer's disease (AD). We employed 18 DLB patients with neocortical Lewy body type pathology (nLBTP) with or without AD. We also employed the same number of AD cases without significant nLBTP. We refer to the former group as the nLBTP group and to the latter as the AD type pathology (ADTP) group. In the nLBTP group, palpha-synuclein positive neurite pathology such as threads and dots occurs in all layers of the temporal neocortex. It was comparable in degree with tau pathology in AD. Fifteen cases in the nLBTP group were associated with Abeta deposition that meets the CERAD plaque score "C" and one case with a score "B". In these plaque-associated cases, the severity of palpha-synuclein pathology was related to the degree of Abeta deposition. In the cases with relatively moderate Abeta deposition, tau pathology was disproportionately mild in the nLBTP group, while the total of tau and palpha-synuclein pathology was proportionate to Abeta deposition in both the nLBTP and ADTP groups. Our results support the ideas that there is an overlap in the pathology between AD and DLB and that Abeta promotes accumulation of both alpha-synuclein and tau. The procession from Abeta to neurite pathology in the cerebral cortex of AD and DLB may be unifiable. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/18164295/Relationship_of_phosphorylated_alpha_synuclein_and_tau_accumulation_to_Abeta_deposition_in_the_cerebral_cortex_of_dementia_with_Lewy_bodies_ DB - PRIME DP - Unbound Medicine ER -