Neuronal thread protein over-expression in brains with Alzheimer's disease lesions.
Neuronal thread protein (NTP) is a recently characterized molecule that is over-expressed in brains with Alzheimer's disease (AD) lesions. The present study encompasses a detailed analysis of NTP expression in AD compared with other neurodegenerative diseases and aged controls. Using a specific monoclonal antibody, NTP immunoreactivity was evaluated in 309 paraffin-embedded sections from 8 different regions of the frontal, parietal, and temporal lobes of 73 brains with AD, AD + Down's syndrome (DN), AD + Parkinson's disease (PD), PD dementia (PDD), aged controls, and disease controls with Huntington's disease, multi-infarct dementia, or schizophrenia. In 250 adjacent blocks of snap-frozen unfixed tissue the concentration of NTP (ng/mg of protein) was measured using a 3-site forward sandwich monoclonal antibody based immunoradiometric assay (M-IRMA). Immunohistochemical studies demonstrated that brains with AD, AD + PD, and AD + DN contained significantly higher densities of NTP immunoreactive neurons and more frequent immunostaining of neuropil and white matter fibers compared with PDD and aged controls (both P < 0.001) which had few or no AD lesions. In addition, the overall mean concentrations of NTP in AD, AD + PD, and AD + DN were significantly higher than in PDD and aged controls (P < 0.005). Greater degrees of NTP immunoreactivity and higher concentrations of the protein in cerebral tissue were significantly correlated with AD diagnosis and abundant neurofibrillary tangles (P < 0.005). The findings suggest that NTP over-expression may serve as a marker for the type of neuronal degeneration that occurs in AD.
de la Monte
S M
SM
Massachusetts General Hospital, Alzheimer's Disease Research Center, Boston.
Wands
J R
JR
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D001923:Brain Chemistry; D001927:Brain Diseases / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015592:Immunoradiometric Assay; D051847:Lithostathine; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000032:analysis*; D009474:Neurons / Q000737:chemistry; D012559:Schizophrenia / Q000378:metabolism
C497612:AD7c-NTP protein, human; D002135:Calcium-Binding Proteins; D051847:Lithostathine; D009419:Nerve Tissue Proteins