Cell-type-specific enhancement of amyloid-beta deposition in a novel presenilin-1 mutation (P117L)
| Autor: | J Kulczycki, Eulalia Badmajew, Eirene Popovitch, Jerzy Wegiel, Wieslaw K. Dowjat, Henryk M. Wisniewski, I. Kuchna, Thomas Wisniewski, Michal Tarnawski |
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| Rok vydání: | 1998 |
| Předmět: |
Adult
Male medicine.medical_specialty Down syndrome Pathology Amyloid Proline Amyloid beta Neuropathology Gene mutation Hippocampus Presenilin Pathology and Forensic Medicine Cellular and Molecular Neuroscience Alzheimer Disease Leucine Internal medicine Cerebellum mental disorders medicine Presenilin-1 Entorhinal Cortex Humans Point Mutation Age of Onset Aged Amyloid beta-Peptides biology Brain Membrane Proteins General Medicine Middle Aged medicine.disease Endocrinology Neurology Dentate Gyrus biology.protein Female Neurology (clinical) Poland Alzheimer's disease Age of onset Down Syndrome |
| Zdroj: | Journal of neuropathology and experimental neurology. 57(9) |
| ISSN: | 0022-3069 |
| Popis: | The presenilin-1 (PS1) gene mutation (Pro117Leu), recently identified in a Polish family is characterized by the earliest reported onset (from 24-31 years) of Alzheimer disease (AD) and a very short duration of disease (4-6 years). The neuropathology of 2 subjects with this PS1 mutation (ages at death: 35 and 37 years) was compared to four Down syndrome (DS) patients (mean age at death: 62 years) and 4 sporadic AD patients (mean age at death: 79 years with a mean duration of disease of 18 years). The Polish familial AD (FAD) patients showed a marked increase in the amyloid burden of 2 6-fold in most areas of the brain. The entorhinal cortex was an exception where the amyloid burden was similar in each category of patient. Some brain regions of the Polish FAD patients showed a massive increase of amyloid, such as the molecular layer of the cerebellum where a 7- and 25-fold increase was noted, compared with DS and sporadic AD patients respectively. The cerebellar vessel amyloid burden was also greatly increased in the FAD patients, reflecting a vascular compartment specific increase of amyloid beta deposition. The presence of this PS1 mutation has an even greater effect on both vascular and parenchymal amyloid deposition, than the overexpression of the amyloid beta precursor protein present in DS patients, suggesting that PS mutations can be a critical factor determining amyloid deposition. |
| Databáze: | OpenAIRE |
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