Localization of Tissue Inhibitor of Matrix Metalloproteinases in Alzheimerʼs Disease and Normal Brain
Abstract
Based upon the hypothesis that metalloproteinases and their inhibitors might be involved in the pathogenesis of Alzheimer's disease, we studied brain samples of eight cases of Alzheimer's disease, six other pathological entities and three elderly controls for tissue inhibitor of metalloproteinase (TIMP) immunoreactivity. Specificity was supported by a loss of immunoreactivity following antigen preabsorption of antisera. Areas studied included ependyma, choroid plexus, frontoparietal, hippocampal and cerebellar cortex, n. basalis of Meynert, basal ganglia, midbrain, pons, and medulla. TIMP positivity was localized to neuritic senile plaques, neurofibrillary tangles and Purkinje cells. The pattern of TIMP plaque staining was similar to that observed with anti tau and SP18 antibodies. It differed from that observed with anti SP40, HAM 56 and GFAP antibodies. The selective localization of TIMP to the neuritic lesions of Alzheimer's disease in a codistribution with the amyloid precursor protein and abnormally phosphorylated and truncated tau supports a possible role for metalloproteinases and their inhibitors in the evolution of these lesions.
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TIMP levels are increased in postmortem brains of AD patients.
“TIMP levels are increased in postmortem brains of AD patients (Peress et al., 1995)”
From The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders (2018) · cites this paper as Peress et al., 1995
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MCGEER, P., & MCGEER, E. (1995) · Brain Research Reviews · doi:10.1016/0165-0173(95)00011-9 · Cited by 1,287 · see citing works
Increased plasma levels of matrix metalloproteinase-9 in patients with Alzheimer’s disease.
Lorenzl, S. (2003) · Neurochemistry International · doi:10.1016/s0197-0186(03)00004-4 · Cited by 243 · see citing works
Extracellular matrix degradation by metalloproteinases and central nervous system diseases
Lukes, A., Mun-Bryce, S., Lukes, M., & Rosenberg, G. A. (1999) · Molecular Neurobiology · doi:10.1007/bf02821717 · Cited by 230 · see citing works
Brkic, M., Balusu, S., Libert, C., & Vandenbroucke, R. E. (2015) · Mediators of Inflammation · doi:10.1155/2015/620581 · Cited by 205 · see citing works
The Perineuronal ‘Safety’ Net? Perineuronal Net Abnormalities in Neurological Disorders
Wen, T. H., Binder, D. K., Ethell, I. M., & Razak, K. A. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00270 · Cited by 170 · see citing works
- Authors
- PERESS, N., PERILLO, E. D., & ZUCKER, S.
- Affiliations
- Veterans Health Administration (US)
- Northport VA Medical Center (US)
- Corresponding author
- PERESS, NANCY
- Venue
- Journal of Neuropathology and Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 1995-01
- Volume
- 54
- Issue
- 1
- Pages
- 16-22
- ISSN
- 0022-3069 (ISSN-L)
- OpenAlex
- W2076979781
- Cited by
- 81
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 3 · 2018: 2 · 2017: 2 · 2016: 3 · 2015: 2 · 2014: 2 · 2013: 3 · 2012: 2
- FWCI
- 1.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- tissue inhibitors of metalloproteinases, Alzheimer's disease, metalloproteinases, neurofibrillary tangles, tau phosphorylation, amyloid precursor protein, Purkinje cells, hippocampus, choroid plexus, basal ganglia, immunolocalization
- MeSH terms
- Aged, Alzheimer Disease, Brain, Central Nervous System Diseases, Extracellular Matrix, Glycoproteins, Humans, Metalloendopeptidases, Reference Values, Tissue Distribution, Neurites, Neurofibrillary Tangles, Tissue Inhibitor of Metalloproteinases
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