CA1 hippocampal neuronal loss in familial Alzheimer's disease presenilin-1 E280A mutation is related to epilepsy.
OBJECTIVE
Alzheimer disease (AD) and epilepsy are brain disorders frequently associated with neuronal cell loss in mesial temporal lobe structures, but presenting different patterns of damage. Recently it was proposed that a causal relation may exist between AD pathology and the appearance of epilepsy in some cases with AD. This study aimed to determine the neuronal loss in CA1 hippocampal region from patients bearing the presenilin-1 [E280A] mutation (PS1[E280A]) associated with seizures.


METHODS
Coronal sections from the hippocampal formation (anterior one third) from controls (n = 5) and familial AD (FAD; n = 8) patients were stained by using thionin and thioflavine-S staining to evaluate the number of neurons in the CA1 field, beta-plaques, and neurofibrillary tangles, respectively.


RESULTS
Two distinct patterns of neuronal loss in the CA1 field of FAD patients were found: (a) diffuse-patchy neuronal loss (three FAD nonepilepsy patients) characterized by both a general decrease of neurons and the presence of multiple, small regions devoid of neurons; and (b) sclerotic-like neuronal loss (five FAD epilepsy patients) similar to that found typically in the CA1 field of epilepsy patients with hippocampal sclerosis.


CONCLUSIONS
This investigation shows for the first time CA1 neuronal depopulation in a subpopulation of patients (five of eight) bearing the PS1[E280A] mutation with epileptic seizures, indicating a relation between hippocampal neuronal loss and epileptic seizures in FAD patients.
Velez-Pardo
Carlos
C
School of Medicine, Internal Medicine, Neuroscience Research Program, University of Antioquia, Medellin, Colombia.
Arellano
Jon I
JI
Cardona-Gomez
Patricia
P
Jimenez Del Rio
Marlene
M
Lopera
Francisco
F
De Felipe
Javier
J
D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D002452:Cell Count; D016923:Cell Death / Q000235:genetics; D015897:Comorbidity; D004827:Epilepsy / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*; D005190:Family; D005260:Female; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D016874:Neurofibrillary Tangles / Q000473:pathology; D009474:Neurons / Q000473:pathology; D058225:Plaque, Amyloid / Q000473:pathology; D053764:Presenilin-1; D017966:Pyramidal Cells / Q000473:pathology
D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1