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Exclusive association and simultaneous appearance of congophilic plaques and AT8-positive dystrophic neurites in Tg2576 mice suggest a mechanism of senile plaque formation and progression of neuritic dystrophy in Alzheimer's disease.
Acta Neuropathol 2004; 108(5):435-42AN

Abstract

Progression of neuritic dystrophy is a histological hallmark of Alzheimer's disease (AD) in addition to amyloid deposition and neurofibrillary tangle formation. Dystrophic neurites (DNs) are abnormal neurites, and are closely associated with amyloid deposits. To clarify the process of DN formation, we immunohistochemically investigated phosphorylated tau (AT8 and Ser396)-positive DNs and plaques in Tg2576 mice overexpressing human beta-amyloid precursor protein (APP) with the Swedish type mutation (K670N/M671L). AT8-positive DNs were exclusively associated with the Congo red-positive plaques examined, and all Abeta(1-40)-positive plaques appeared to be associated with AT8-positive DNs, whereas there were no AT8-positive DNs with Abeta(1-42)-positive/Abeta(1-40)-negative plaques. Since we have previously shown that Abeta(1-42)-positive plaque precede Abeta(1-40) deposition, the appearance of congophilic structures is also late. Quantitative analyses were performed on AT8-positive DNs that were associated with congophilic plaques in the cerebral cortex and hippocampus (more than 1,000 plaques). The number of congophilic plaques increased dramatically with age. The area of DNs in the cerebral cortex and hippocampus increased 120- and 60-fold from 11-13 to 20.5 months of age, respectively. Interestingly, the mean ratio of DN area to congophilic plaque area in every plaque was unchanged, approximately 10%, through the ages examined. The mean plaque size was stable with age in both the cortex and hippocampus. These data suggest that the formation of AT8-positive DNs is simultaneous with Congo red-positive plaque development, and that the event may be closely related in the pathological progression of AD.

Authors+Show Affiliations

Neuroscience Research, Yamanouchi Pharmaceutical Company Limited, 21 Miyukigaoka, Tsukuba, 305-8585 Ibaraki, Japan. nodak@yamanouchi.co.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15372280

Citation

Noda-Saita, Kyoko, et al. "Exclusive Association and Simultaneous Appearance of Congophilic Plaques and AT8-positive Dystrophic Neurites in Tg2576 Mice Suggest a Mechanism of Senile Plaque Formation and Progression of Neuritic Dystrophy in Alzheimer's Disease." Acta Neuropathologica, vol. 108, no. 5, 2004, pp. 435-42.
Noda-Saita K, Terai K, Iwai A, et al. Exclusive association and simultaneous appearance of congophilic plaques and AT8-positive dystrophic neurites in Tg2576 mice suggest a mechanism of senile plaque formation and progression of neuritic dystrophy in Alzheimer's disease. Acta Neuropathol. 2004;108(5):435-42.
Noda-Saita, K., Terai, K., Iwai, A., Tsukamoto, M., Shitaka, Y., Kawabata, S., ... Yamaguchi, T. (2004). Exclusive association and simultaneous appearance of congophilic plaques and AT8-positive dystrophic neurites in Tg2576 mice suggest a mechanism of senile plaque formation and progression of neuritic dystrophy in Alzheimer's disease. Acta Neuropathologica, 108(5), pp. 435-42.
Noda-Saita K, et al. Exclusive Association and Simultaneous Appearance of Congophilic Plaques and AT8-positive Dystrophic Neurites in Tg2576 Mice Suggest a Mechanism of Senile Plaque Formation and Progression of Neuritic Dystrophy in Alzheimer's Disease. Acta Neuropathol. 2004;108(5):435-42. PubMed PMID: 15372280.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Exclusive association and simultaneous appearance of congophilic plaques and AT8-positive dystrophic neurites in Tg2576 mice suggest a mechanism of senile plaque formation and progression of neuritic dystrophy in Alzheimer's disease. AU - Noda-Saita,Kyoko, AU - Terai,Kazuhiro, AU - Iwai,Akihiko, AU - Tsukamoto,Mina, AU - Shitaka,Yoshitsugu, AU - Kawabata,Shigeki, AU - Okada,Masamichi, AU - Yamaguchi,Tokio, Y1 - 2004/09/14/ PY - 2004/03/11/received PY - 2004/06/25/revised PY - 2004/06/28/accepted PY - 2004/9/17/pubmed PY - 2005/2/3/medline PY - 2004/9/17/entrez SP - 435 EP - 42 JF - Acta neuropathologica JO - Acta Neuropathol. VL - 108 IS - 5 N2 - Progression of neuritic dystrophy is a histological hallmark of Alzheimer's disease (AD) in addition to amyloid deposition and neurofibrillary tangle formation. Dystrophic neurites (DNs) are abnormal neurites, and are closely associated with amyloid deposits. To clarify the process of DN formation, we immunohistochemically investigated phosphorylated tau (AT8 and Ser396)-positive DNs and plaques in Tg2576 mice overexpressing human beta-amyloid precursor protein (APP) with the Swedish type mutation (K670N/M671L). AT8-positive DNs were exclusively associated with the Congo red-positive plaques examined, and all Abeta(1-40)-positive plaques appeared to be associated with AT8-positive DNs, whereas there were no AT8-positive DNs with Abeta(1-42)-positive/Abeta(1-40)-negative plaques. Since we have previously shown that Abeta(1-42)-positive plaque precede Abeta(1-40) deposition, the appearance of congophilic structures is also late. Quantitative analyses were performed on AT8-positive DNs that were associated with congophilic plaques in the cerebral cortex and hippocampus (more than 1,000 plaques). The number of congophilic plaques increased dramatically with age. The area of DNs in the cerebral cortex and hippocampus increased 120- and 60-fold from 11-13 to 20.5 months of age, respectively. Interestingly, the mean ratio of DN area to congophilic plaque area in every plaque was unchanged, approximately 10%, through the ages examined. The mean plaque size was stable with age in both the cortex and hippocampus. These data suggest that the formation of AT8-positive DNs is simultaneous with Congo red-positive plaque development, and that the event may be closely related in the pathological progression of AD. SN - 0001-6322 UR - https://www.unboundmedicine.com/medline/citation/15372280/Exclusive_association_and_simultaneous_appearance_of_congophilic_plaques_and_AT8_positive_dystrophic_neurites_in_Tg2576_mice_suggest_a_mechanism_of_senile_plaque_formation_and_progression_of_neuritic_dystrophy_in_Alzheimer's_disease_ L2 - https://dx.doi.org/10.1007/s00401-004-0907-2 DB - PRIME DP - Unbound Medicine ER -