TY - JOUR
T1 - Specific amyloid-β42 deposition in the brain of a Gerstmann-Sträussler-Scheinker disease patient with a P105L mutation on the prion protein gene
AU - Furukawa, Fumiko
AU - Sanjo, Nobuo
AU - Kobayashi, Atsushi
AU - Hamaguchi, Tsuyoshi
AU - Yamada, Masahito
AU - Kitamoto, Tetsuyuki
AU - Mizusawa, Hidehiro
AU - Yokota, Takanori
N1 - Funding Information:
This work was supported by a Grant-in-Aid from the Research Committee of Prion Disease and Slow Virus Infection of the Ministry of Health, Labour, and Welfare of Japan (AK, TH, MY, TK, HM, and NS); a Grant-in-Aid from the Research Committee of Molecular Pathogenesis and Therapies for Prion Disease and Slow Virus Infection (AK, TH, MY, TK, and HM); and a Grant-in-Aid from the Research Committee of Surveillance and Infection Control of Prion Disease of the Ministry of Health, Labour, and Welfare of Japan (KS, MY, TK, HM, and NS).
Funding Information:
This work was supported by a Grant-in-Aid from the Research Committee of Prion Disease and Slow Virus Infection of the Ministry of Health, Labour, and Welfare of Japan (AK, TH, MY, TK, HM, and NS); a Grant-in-Aid from the Research Committee of Molecular Pathogenesis and Therapies for Prion Disease and Slow Virus Infection (AK, TH, MY, TK, and HM); and a Grant-in-Aid from the Research Committee of Surveillance and Infection Control of Prion Disease of the Ministry of Health, Labour, and Welfare of Japan (KS, MY, TK, HM, and NS). The authors thank members of the Department of Neurology and Neurological Science, Tokyo Medical and Dental University hospital, as well as the patient and her family members for providing important clinical information. We are grateful to the member of the Department of Neurology and Neurobiology of Aging, Kanazawa University Graduate School of Medical Science and the Department of Neurological Science, Tohoku University Graduate School of Medicine for their technical assistance.
Publisher Copyright:
© 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2018/11/2
Y1 - 2018/11/2
N2 - Although colocalization of amyloid β (Aβ) with prion protein (PrP) in the kuru plaque has previously been observed in the brain of prion diseases patients, the participating Aβ species has not been identified. Here, we present an immunohistochemical assessment of the brain and spinal cord of a 69-year-old Japanese female patient with Gerstmann-Sträussler-Scheinker disease with a P105L mutation on the PRNP gene (GSS-P105L). Immunohistochemical assessment of serial brain sections was performed using anti-PrP and -Aβ antibodies in the hippocampus, frontal and occipital lobes. She died 69 years after a 21-year clinical course. Immunohistochemistorical examination revealed that ~50% of the kuru plaques in the cerebrum were colocalized with Aβ, and Aβ42 was predominantly observed to be colocalized with PrP-plaques. The Aβ deposition patterns were unique, and distinct from diffuse plaques observed in the normal aging brain or Alzheimer’s disease brain. The spinal cord exhibited degeneration in the lateral corticospinal tract, posterior horn, and fasciculus gracilis. We have demonstrated for the first time that Aβ42, rather than Aβ40, is the main Aβ component associated with PrP-plaques, and also the degeneration of the fasciculus gracilis in the spinal cord in GSS-P105L, which could be associated with specific clinical features of GSS-P105L.
AB - Although colocalization of amyloid β (Aβ) with prion protein (PrP) in the kuru plaque has previously been observed in the brain of prion diseases patients, the participating Aβ species has not been identified. Here, we present an immunohistochemical assessment of the brain and spinal cord of a 69-year-old Japanese female patient with Gerstmann-Sträussler-Scheinker disease with a P105L mutation on the PRNP gene (GSS-P105L). Immunohistochemical assessment of serial brain sections was performed using anti-PrP and -Aβ antibodies in the hippocampus, frontal and occipital lobes. She died 69 years after a 21-year clinical course. Immunohistochemistorical examination revealed that ~50% of the kuru plaques in the cerebrum were colocalized with Aβ, and Aβ42 was predominantly observed to be colocalized with PrP-plaques. The Aβ deposition patterns were unique, and distinct from diffuse plaques observed in the normal aging brain or Alzheimer’s disease brain. The spinal cord exhibited degeneration in the lateral corticospinal tract, posterior horn, and fasciculus gracilis. We have demonstrated for the first time that Aβ42, rather than Aβ40, is the main Aβ component associated with PrP-plaques, and also the degeneration of the fasciculus gracilis in the spinal cord in GSS-P105L, which could be associated with specific clinical features of GSS-P105L.
KW - Amyloid-β42
KW - Gerstmann-Sträussler-Scheinker disease
KW - P105L
KW - colocalization
KW - fasciculus gracili
KW - prion protein
UR - http://www.scopus.com/inward/record.url?scp=85056530909&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85056530909&partnerID=8YFLogxK
U2 - 10.1080/19336896.2018.1541689
DO - 10.1080/19336896.2018.1541689
M3 - Article
C2 - 30394185
AN - SCOPUS:85056530909
VL - 12
SP - 315
EP - 319
JO - Prion
JF - Prion
SN - 1933-6896
IS - 5-6
ER -