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The Arctic amyloid-β precursor protein (AβPP) mutation results in distinct plaques and accumulation of N- and C-truncated Aβ.
Neurobiol Aging. 2012 May; 33(5):1010.e1-13.NA

Abstract

The Arctic (p. E693G) mutation in the amyloid-β precursor protein (AβPP) facilitates amyloid-β (Aβ) protofibril formation and generates clinical symptoms of Alzheimer's disease (AD). Here, molecular details of Aβ in post mortem brain were investigated with biochemical and morphological techniques. The basic structure of Arctic plaques resembled cotton wool plaques. However, they appeared ring-formed with Aβ42-specific antibodies, but were actually targetoid, since the periphery and center of many parenchymal Aβ deposits stained differently with mid-domain, N- and C-terminal Aβ antibodies. Aβ fibrils were similar in shape, albeit shorter than in sporadic AD brain, when examined by electron microscopy. Aβwild-type and Aβarctic codeposited and parenchymal deposits were highly enriched in both N- and C-terminally truncated Aβ. In contrast, cerebral amyloid angiopathy (CAA) contained a substantial amount of Aβ1-40. The absence of plaques with cores of fibrillary Aβ might be due to the scarcity of full-length Aβ, although other mechanisms could be involved. Our findings are discussed in relation to mechanisms and relevance of amyloid formation and to the clinical features of AD.

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Authors+Show Affiliations

Philipson O
Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden.
Lord A
No affiliation info available
Lalowski M
No affiliation info available
Soliymani R
No affiliation info available
Baumann M
No affiliation info available
Thyberg J
No affiliation info available
Bogdanovic N
No affiliation info available
Olofsson T
No affiliation info available
Tjernberg LO
No affiliation info available
Ingelsson M
No affiliation info available
Lannfelt L
No affiliation info available
Kalimo H
No affiliation info available
Nilsson LN
No affiliation info available

MeSH

AgedAlzheimer DiseaseAmino Acid SubstitutionAmyloid beta-PeptidesAmyloid beta-Protein PrecursorFemaleHumansMaleMiddle AgedMolecular WeightPeptide FragmentsPlaque, AmyloidProtein IsoformsProtein Structure, Tertiary

Pub Type(s)

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

Language

eng

PubMed ID

22118948

Citation

Philipson, Ola, et al. "The Arctic Amyloid-β Precursor Protein (AβPP) Mutation Results in Distinct Plaques and Accumulation of N- and C-truncated Aβ." Neurobiology of Aging, vol. 33, no. 5, 2012, pp. 1010.e1-13.
Philipson O, Lord A, Lalowski M, et al. The Arctic amyloid-β precursor protein (AβPP) mutation results in distinct plaques and accumulation of N- and C-truncated Aβ. Neurobiol Aging. 2012;33(5):1010.e1-13.
Philipson, O., Lord, A., Lalowski, M., Soliymani, R., Baumann, M., Thyberg, J., Bogdanovic, N., Olofsson, T., Tjernberg, L. O., Ingelsson, M., Lannfelt, L., Kalimo, H., & Nilsson, L. N. (2012). The Arctic amyloid-β precursor protein (AβPP) mutation results in distinct plaques and accumulation of N- and C-truncated Aβ. Neurobiology of Aging, 33(5), e1-13. https://doi.org/10.1016/j.neurobiolaging.2011.10.022
Philipson O, et al. The Arctic Amyloid-β Precursor Protein (AβPP) Mutation Results in Distinct Plaques and Accumulation of N- and C-truncated Aβ. Neurobiol Aging. 2012;33(5):1010.e1-13. PubMed PMID: 22118948.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The Arctic amyloid-β precursor protein (AβPP) mutation results in distinct plaques and accumulation of N- and C-truncated Aβ. AU - Philipson,Ola, AU - Lord,Anna, AU - Lalowski,Maciej, AU - Soliymani,Rabah, AU - Baumann,Marc, AU - Thyberg,Johan, AU - Bogdanovic,Nenad, AU - Olofsson,Tommie, AU - Tjernberg,Lars O, AU - Ingelsson,Martin, AU - Lannfelt,Lars, AU - Kalimo,Hannu, AU - Nilsson,Lars N G, Y1 - 2011/11/26/ PY - 2011/09/23/received PY - 2011/10/18/revised PY - 2011/10/21/accepted PY - 2011/11/29/entrez PY - 2011/11/29/pubmed PY - 2012/12/10/medline SP - 1010.e1 EP - 13 JF - Neurobiology of aging JO - Neurobiol Aging VL - 33 IS - 5 N2 - The Arctic (p. E693G) mutation in the amyloid-β precursor protein (AβPP) facilitates amyloid-β (Aβ) protofibril formation and generates clinical symptoms of Alzheimer's disease (AD). Here, molecular details of Aβ in post mortem brain were investigated with biochemical and morphological techniques. The basic structure of Arctic plaques resembled cotton wool plaques. However, they appeared ring-formed with Aβ42-specific antibodies, but were actually targetoid, since the periphery and center of many parenchymal Aβ deposits stained differently with mid-domain, N- and C-terminal Aβ antibodies. Aβ fibrils were similar in shape, albeit shorter than in sporadic AD brain, when examined by electron microscopy. Aβwild-type and Aβarctic codeposited and parenchymal deposits were highly enriched in both N- and C-terminally truncated Aβ. In contrast, cerebral amyloid angiopathy (CAA) contained a substantial amount of Aβ1-40. The absence of plaques with cores of fibrillary Aβ might be due to the scarcity of full-length Aβ, although other mechanisms could be involved. Our findings are discussed in relation to mechanisms and relevance of amyloid formation and to the clinical features of AD. SN - 1558-1497 UR - https://www.unboundmedicine.com/medline/citation/22118948/The_Arctic_amyloid_β_precursor_protein__AβPP__mutation_results_in_distinct_plaques_and_accumulation_of_N__and_C_truncated_Aβ_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-4580(11)00453-2 DB - PRIME DP - Unbound Medicine ER -