Laminar specific loss of isocortical presenilin 1 immunoreactivity in Alzheimer's disease. Correlations with the amyloid load and the density of tau-positive neurofibrillary tangles.
Presenilin 1 has been shown to be mutated in a high proportion of cases of familial Alzheimer's disease. Immunoreactive epitopes of the protein have been found mainly in neurones devoid of neurofibrillary tangles - an observation that has led to the conclusion that presenilin 1 could have a protective role. In this study, the relationship between deposits of Abeta peptide (both the 40 and 42 isoforms), tau positive neurofibrillary tangles and presenilin 1-positive neuronal profiles were analysed in three cases of presenilin 1 mutation, four cases of sporadic Alzheimer's disease and five controls. Immunohistochemistry was performed in a sample from the supramarginal gyrus. The proportion of volume occupied by the Abeta1-40 and Abeta1-42 deposits (amyloid load) was evaluated by a point-counting technique. Tau-positive neurofibrillary tangles, and presenilin 1-positive neuronal profiles were directly counted. The location of the lesions in the thickness of the cortex was recorded. The density of PS1-positive neuronal profiles in Alzheimer's disease cases was lower than in the controls. The deficit was significant only in the upper layers of the cortex. The density of presenilin 1 neuronal profiles was negatively correlated with Abeta1-40 and Abeta1-42 loads, and with the density of tau-positive neurofibrillary tangles. Multivariate analysis showed that the Abeta1-42 load was the best determinant of the decrease in presenilin 1-positive neuronal profiles. Presenilin 1-positive neurones appear to be lost rather than protected in the course of Alzheimer disease.
Colle
M A
MA
Laboratoire de Neuropathologie R. Escourolle, GH Pitié-Salpêtrière, INSERM U106 and U360 Association Claude Bernard, Paris, France.
Duyckaerts
C
C
Laquerrière
A
A
Pradier
L
L
Czech
C
C
Checler
F
F
Hauw
J J
JJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000276:immunology; D000686:Amyloidosis / Q000473:pathology; D000906:Antibodies; D002540:Cerebral Cortex / Q000737:chemistry / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000032:analysis* / Q000276:immunology; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000737:chemistry / Q000473:pathology*; D009474:Neurons / Q000737:chemistry / Q000473:pathology; D053764:Presenilin-1; D016875:tau Proteins / Q000032:analysis* / Q000276:immunology
D016229:Amyloid beta-Peptides; D000906:Antibodies; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D016875:tau Proteins