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Quantification of molecular interactions between ApoE, amyloid-beta (A?) and laminin: relevance to accumulation of A? in Alzheimer's disease

Quantification of molecular interactions between ApoE, amyloid-beta (A?) and laminin: relevance to accumulation of A? in Alzheimer's disease
Quantification of molecular interactions between ApoE, amyloid-beta (A?) and laminin: relevance to accumulation of A? in Alzheimer's disease
Accumulation of amyloid-? (A?) in plaques in the brain and in artery walls as cerebral amyloid angiopathy indicates a failure of elimination of A? from the brain with age and Alzheimer's disease. A major pathway for elimination of A? and other soluble metabolites from the brain is along basement membranes within the walls of cerebral arteries that represent the lymphatic drainage pathways for the brain. The motive force for the elimination of A? along this perivascular pathway appears to be the contrary (reflection) wave that follows the arterial pulse wave. Following injection into brain parenchyma, A? rapidly drains out of the brain along basement membranes in the walls of cerebral arteries; such drainage is impaired in apolipoprotein E ?4 (ApoE4) mice. For drainage of A? to occur in a direction contrary to the pulse wave, some form of attachment to basement membrane would be required to prevent reflux of A? back into the brain during the passage of the subsequent pulse wave. In this study, we show first that apolipoprotein E co-localizes with A? in basement membrane drainage pathways in the walls of arteries. Secondly, we show by Atomic Force Microscopy that attachment of ApoE4/A? complexes to basement membrane laminin is significantly weaker than ApoE3/A? complexes. These results suggest that perivascular elimination of ApoE4/A? complexes would be less efficient than with other isoforms of apolipoprotein E, thus endowing a higher risk for Alzheimer's disease. Therapeutic correction for ApoE4/A?/laminin interactions may increase the efficiency of elimination of A? in the prevention of Alzheimer's disease.
apolipoprotein E, perivascular clearance pathways, laminin, atomic force microscopy, amyloid-?, cerebral amyloid angiopathy, alzheimer's disease
0925-4439
1-7
Zekonyte, Jurgita
51de4316-3f4b-4a32-864f-fcfe1b510b17
Sakai, Kenji
3e0ffcfa-b63d-420e-a49c-4533fbacd58b
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Weller, Roy O.
4a501831-e38a-4d39-a125-d7141d6c667b
Carare, Roxana O.
0478c197-b0c1-4206-acae-54e88c8f21fa
Zekonyte, Jurgita
51de4316-3f4b-4a32-864f-fcfe1b510b17
Sakai, Kenji
3e0ffcfa-b63d-420e-a49c-4533fbacd58b
Nicoll, James A.R.
88c0685f-000e-4eb7-8f72-f36b4985e8ed
Weller, Roy O.
4a501831-e38a-4d39-a125-d7141d6c667b
Carare, Roxana O.
0478c197-b0c1-4206-acae-54e88c8f21fa

Zekonyte, Jurgita, Sakai, Kenji, Nicoll, James A.R., Weller, Roy O. and Carare, Roxana O. (2015) Quantification of molecular interactions between ApoE, amyloid-beta (A?) and laminin: relevance to accumulation of A? in Alzheimer's disease. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1-7. (doi:10.1016/j.bbadis.2015.08.025). (PMID:26327683)

Record type: Article

Abstract

Accumulation of amyloid-? (A?) in plaques in the brain and in artery walls as cerebral amyloid angiopathy indicates a failure of elimination of A? from the brain with age and Alzheimer's disease. A major pathway for elimination of A? and other soluble metabolites from the brain is along basement membranes within the walls of cerebral arteries that represent the lymphatic drainage pathways for the brain. The motive force for the elimination of A? along this perivascular pathway appears to be the contrary (reflection) wave that follows the arterial pulse wave. Following injection into brain parenchyma, A? rapidly drains out of the brain along basement membranes in the walls of cerebral arteries; such drainage is impaired in apolipoprotein E ?4 (ApoE4) mice. For drainage of A? to occur in a direction contrary to the pulse wave, some form of attachment to basement membrane would be required to prevent reflux of A? back into the brain during the passage of the subsequent pulse wave. In this study, we show first that apolipoprotein E co-localizes with A? in basement membrane drainage pathways in the walls of arteries. Secondly, we show by Atomic Force Microscopy that attachment of ApoE4/A? complexes to basement membrane laminin is significantly weaker than ApoE3/A? complexes. These results suggest that perivascular elimination of ApoE4/A? complexes would be less efficient than with other isoforms of apolipoprotein E, thus endowing a higher risk for Alzheimer's disease. Therapeutic correction for ApoE4/A?/laminin interactions may increase the efficiency of elimination of A? in the prevention of Alzheimer's disease.

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Accepted/In Press date: 26 August 2015
e-pub ahead of print date: 29 August 2015
Keywords: apolipoprotein E, perivascular clearance pathways, laminin, atomic force microscopy, amyloid-?, cerebral amyloid angiopathy, alzheimer's disease
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 383082
URI: https://eprints.soton.ac.uk/id/eprint/383082
ISSN: 0925-4439
PURE UUID: 15469f1d-f10e-4512-9d43-54a74eff4f14
ORCID for James A.R. Nicoll: ORCID iD orcid.org/0000-0002-9444-7246

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Date deposited: 20 Oct 2015 12:03
Last modified: 06 Jun 2018 12:49

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