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Abnormal neurites containing C-terminally truncated alpha-synuclein are present in Alzheimer's disease without conventional Lewy body pathology.Am J Pathol. 2010 Dec; 177(6):3037-50.AJ
Abstract
The pathological hallmark of Parkinson's disease and diffuse Lewy body disease (DLBD) is the aggregation of α-synuclein (α-syn) in the form of Lewy bodies and Lewy neurites. Patients with both Alzheimer's disease (AD) and cortical Lewy pathology represent the Lewy body variant of AD (LBV) and constitute 25% of AD cases. C-terminally truncated forms of α-syn enhance the aggregation of α-syn in vitro. To investigate the presence of C-terminally truncated α-syn in DLBD, AD, and LBV, we generated and validated polyclonal antibodies to truncated α-syn ending at residues 110 (α-syn110) and 119 (α-syn119), two products of 20S proteosome-mediated endoproteolytic cleavage. Double immunofluorescence staining of the cingulate cortex showed that α-syn110 and α-syn140 (full-length) aggregates were not colocalized in LBV. All aggregates containing α-syn140 also contained α-syn119; however, some aggregates contained α-syn119 without α-syn140, suggesting that α-syn119 may stimulate aggregate formation. Immunohistochemistry and image analysis of tissue microarrays of the cingulate cortex from patients with DLBD (n = 27), LBV (n = 27), and AD (n = 19) and age-matched controls (n = 15) revealed that AD is also characterized by frequent abnormal neurites containing α-syn119. Notably, these neurites did not contain α-syn ending at residues 110 or 122-140. The presence of abnormal neurites containing α-syn119 in AD without conventional Lewy pathology suggests that AD and Lewy body disease may be more closely related than previously thought.
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MeSH
Pub Type(s)
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Language
eng
PubMed ID
21056999
Citation
Lewis, Karen A., et al. "Abnormal Neurites Containing C-terminally Truncated Alpha-synuclein Are Present in Alzheimer's Disease Without Conventional Lewy Body Pathology." The American Journal of Pathology, vol. 177, no. 6, 2010, pp. 3037-50.
Lewis KA, Su Y, Jou O, et al. Abnormal neurites containing C-terminally truncated alpha-synuclein are present in Alzheimer's disease without conventional Lewy body pathology. Am J Pathol. 2010;177(6):3037-50.
Lewis, K. A., Su, Y., Jou, O., Ritchie, C., Foong, C., Hynan, L. S., White, C. L., Thomas, P. J., & Hatanpaa, K. J. (2010). Abnormal neurites containing C-terminally truncated alpha-synuclein are present in Alzheimer's disease without conventional Lewy body pathology. The American Journal of Pathology, 177(6), 3037-50. https://doi.org/10.2353/ajpath.2010.100552
Lewis KA, et al. Abnormal Neurites Containing C-terminally Truncated Alpha-synuclein Are Present in Alzheimer's Disease Without Conventional Lewy Body Pathology. Am J Pathol. 2010;177(6):3037-50. PubMed PMID: 21056999.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR
T1 - Abnormal neurites containing C-terminally truncated alpha-synuclein are present in Alzheimer's disease without conventional Lewy body pathology.
AU - Lewis,Karen A,
AU - Su,Yang,
AU - Jou,Olina,
AU - Ritchie,Caroline,
AU - Foong,Chan,
AU - Hynan,Linda S,
AU - White,Charles L,3rd
AU - Thomas,Philip J,
AU - Hatanpaa,Kimmo J,
Y1 - 2010/11/05/
PY - 2010/11/9/entrez
PY - 2010/11/9/pubmed
PY - 2011/3/16/medline
SP - 3037
EP - 50
JF - The American journal of pathology
JO - Am J Pathol
VL - 177
IS - 6
N2 - The pathological hallmark of Parkinson's disease and diffuse Lewy body disease (DLBD) is the aggregation of α-synuclein (α-syn) in the form of Lewy bodies and Lewy neurites. Patients with both Alzheimer's disease (AD) and cortical Lewy pathology represent the Lewy body variant of AD (LBV) and constitute 25% of AD cases. C-terminally truncated forms of α-syn enhance the aggregation of α-syn in vitro. To investigate the presence of C-terminally truncated α-syn in DLBD, AD, and LBV, we generated and validated polyclonal antibodies to truncated α-syn ending at residues 110 (α-syn110) and 119 (α-syn119), two products of 20S proteosome-mediated endoproteolytic cleavage. Double immunofluorescence staining of the cingulate cortex showed that α-syn110 and α-syn140 (full-length) aggregates were not colocalized in LBV. All aggregates containing α-syn140 also contained α-syn119; however, some aggregates contained α-syn119 without α-syn140, suggesting that α-syn119 may stimulate aggregate formation. Immunohistochemistry and image analysis of tissue microarrays of the cingulate cortex from patients with DLBD (n = 27), LBV (n = 27), and AD (n = 19) and age-matched controls (n = 15) revealed that AD is also characterized by frequent abnormal neurites containing α-syn119. Notably, these neurites did not contain α-syn ending at residues 110 or 122-140. The presence of abnormal neurites containing α-syn119 in AD without conventional Lewy pathology suggests that AD and Lewy body disease may be more closely related than previously thought.
SN - 1525-2191
UR - https://www.unboundmedicine.com/medline/citation/21056999/Abnormal_neurites_containing_C_terminally_truncated_alpha_synuclein_are_present_in_Alzheimer's_disease_without_conventional_Lewy_body_pathology_
L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9440(10)62928-8
DB - PRIME
DP - Unbound Medicine
ER -
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