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Am J Neurodegener Dis. 2014 Mar 28;3(1):19-32. eCollection 2014.

Development, appraisal, validation and implementation of a consensus protocol for the assessment of cerebral amyloid angiopathy in post-mortem brain tissue.

Author information

1
Dementia Research Group, School of Clinical Sciences, University of Bristol,Frenchay Hospital UK.
2
Sheffield Institute for Translational Neuroscience, University of Sheffield UK.
3
Department of Clinical Neurology, University of Oxford UK ; Department of Neuropathology, Oxford Radcliffe NHS Trust UK.
4
Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne UK.
5
Institute of Clinical Neurobiology Vienna, Austria.
6
Department of Neurology and Neurobiology and Aging Kanazawa, Japan.
7
Department of Neurology, Royal Altnagelvin Hospital Derry, UK.
8
Department of Public Health and Primary Care, University of Cambridge UK.
9
MRC Biostatistics Unit, Institute of Public Health Cambridge, UK.
10
Harvard Medical School, Massachusetts General Hospital Boston, USA.
11
Mental Health and Neurodegeneration Research Group Manchester, UK.

Abstract

In a collaboration involving 11 groups with research interests in cerebral amyloid angiopathy (CAA), we used a two-stage process to develop and in turn validate a new consensus protocol and scoring scheme for the assessment of CAA and associated vasculopathic abnormalities in post-mortem brain tissue. Stage one used an iterative Delphi-style survey to develop the consensus protocol. The resultant scoring scheme was tested on a series of digital images and paraffin sections that were circulated blind to a number of scorers. The scoring scheme and choice of staining methods were refined by open-forum discussion. The agreed protocol scored parenchymal and meningeal CAA on a 0-3 scale, capillary CAA as present/absent and vasculopathy on 0-2 scale, in the 4 cortical lobes that were scored separately. A further assessment involving three centres was then undertaken. Neuropathologists in three centres (Bristol, Oxford and Sheffield) independently scored sections from 75 cases (25 from each centre) and high inter-rater reliability was demonstrated. Stage two used the results of the three-centre assessment to validate the protocol by investigating previously described associations between APOE genotype (previously determined), and both CAA and vasculopathy. Association of capillary CAA with or without arteriolar CAA with APOE ε4 was confirmed. However APOE ε2 was also found to be a strong risk factor for the development of CAA, not only in AD but also in elderly non-demented controls. Further validation of this protocol and scoring scheme is encouraged, to aid its wider adoption to facilitate collaborative and replication studies of CAA.

KEYWORDS:

APOE; Angiopathy; CAA; Delphi; amyloid; consensus; dementia; meningeal; parenchymal; validation

PMID:
24754000
PMCID:
PMC3986608
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