We have utilised laser confocal microscopy to categorise β-amyloid plaque types that are associated with preclinical and end-stage Alzheimer's disease and to define the neurochemistry of dystrophic neurites associated with various forms of plaques. Plaques with a spherical profile were defined as either diffuse, fibrillar or dense-cored using Thioflavin S staining or immunolabelling for β-amyloid. Confocal analysis demonstrated that fibrillar plaques had a central mass of β-amyloid with compact spoke-like extensions leading to a confluent outer rim. Dense-cored plaques had a compacted central mass surrounded by an outer sphere of β-amyloid. Diffuse plaques lacked a morphologically identifiable substructure, resembling a ball of homogeneous labelling. The relative proportion of diffuse, fibrillar and dense-cored plaques was 53, 22 and 25% in preclinical and 31, 49 and 20% in end-stage Alzheimer's disease cases, respectively. Plaque-associated dystrophic neurites in preclinical cases were immunolabelled for neurofilament proteins whereas, in end-stage cases, these abnormal neurites were variably labelled for tau and/or neurofilaments. Double labelling demonstrated that the proportion of diffuse, fibrillar and dense-cored plaques that were neuritic was 12, 47 and 82% and 24, 82 and 76% in preclinical and end-stage cases, respectively. Most dystrophic neurites in Alzheimer's disease cases were labelled for either neurofilaments or tau, however, confocal analysis determined that 30% of neurofilament-labelled bulb-like or elongated neurites had a core of tau immunoreactivity. These results indicate that all morphologically defined β-amyloid plaque variants were present in both early and late stages of Alzheimer's disease. However, progression to clinical dementia was associated with both a shift to a higher proportion of fibrillar plaques that induced local neuritic alterations and a transformation of cytoskeletal proteins within associated abnormal neuronal processes. There data indicate key pathological changes that may be subject to therapeutic intervention to slow the progression of Alzheimer's disease. © 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.

Item Type:	Refereed Article
Research Division:	Medical and Health Sciences
Research Group:	Neurosciences
Research Field:	Cellular Nervous System
Objective Division:	Health
Objective Group:	Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:	Nervous System and Disorders
UTAS Author:	Dickson, TC (Professor Tracey Dickson)
UTAS Author:	Vickers, JC (Professor James Vickers)
ID Code:	23464
Year Published:	2001
Web of Science® Times Cited:	139
Deposited By:	Pathology
Deposited On:	2001-08-01
Last Modified:	2002-05-23
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