title: Diagnostic utility of quantitating neurofilament-immunoreactive Alzheimer's disease lesions.
abstract: The diagnosis of Alzheimer's disease (AD) neurodegeneration is based on histopathological detection of paired helical filament-associated lesions. Silver stains are routinely used but the results are fraught with intra- and interinstitutional variability. This study employed monoclonal antibodies to middle and high molecular weight neurofilament subunits in an immunohistochemical assay to assess the extent of paired helical filament-associated lesions in brains with AD, Down's syndrome plus AD lesions (AD+DN), Parkinson's disease dementia (PD), AD+PD, and normal aging changes. The densities of neurofilament-immunoreactive (NFI) cortical neurofibrillary tangles and plaques were significantly higher in AD and AD+DN than in PD and aged control brains (p < 0.001), and NFI neurofibrillary tangles and plaques were more abundant in AD and AD+DN compared with AD+PD and PD, yet all patients with AD, AD+PD, or PD died with end-stage dementia. In contrast, the densities of NFI dystrophic neurites (primarily dendrites) in cortical Layer 2 were similar among the AD, AD+DN, AD+PD, and PD groups, and all were significantly higher than control (p < 0.005). Stepwise multivariate regression analysis demonstrated significant correlations between AD diagnosis and high densities of NFI neurofibrillary tangles and plaques (p < 0.001) and between end-stage AD-type dementia and high densities of NFI dystrophic neurites (p < 0.001). This study demonstrates that the histopathological lesions correlated with AD dementia can be readily detected and quantified by immunostaining with monoclonal antibodies to phosphorylated and non-phosphorylated neurofilaments. Moreover, the findings suggest that NFI neurite pathology may be an important feature contributing to the clinically manifested AD-type dementia in individuals with Parkinson's disease.
authors.affiliation: MGH Alzheimer's Disease Research Center, Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston.
authors.forename: S M
authors.initials: SM
authors.lastname: de la Monte
authors.forename: J R
authors.initials: JR
authors.lastname: Wands
mesh_terms: D000368:Aged; D000375:Aging / Q000378:metabolism / Q000473:pathology; D000544:Alzheimer Disease / Q000150:complications / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D000911:Antibodies, Monoclonal; D001369:Axons / Q000737:chemistry; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D003937:Diagnosis, Differential; D004314:Down Syndrome / Q000150:complications / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D016501:Neurites / Q000737:chemistry* / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000737:chemistry* / Q000473:pathology; D016900:Neurofilament Proteins / Q000032:analysis* / Q000276:immunology; D009474:Neurons / Q000737:chemistry* / Q000473:pathology; D010300:Parkinson Disease / Q000150:complications / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D016900:Neurofilament Proteins