Increased proliferation reflects glial and vascular-associated changes, but not neurogenesis in the presenile Alzheimer hippocampus.
Adult proliferation and hippocampal neurogenesis are stimulated by injury. In agreement, aberrant cell-cycle-related protein expression has been reported in senile Alzheimer's disease (AD), where the hippocampus is particularly affected. Recently, increased expression of doublecortin (DCX), a neurogenesis marker, was reported in senile AD. Here, we addressed whether proliferative and neurogenic responses also occur in younger, i.e., presenile AD cases, using immunohistochemistry for Ki-67, GFAP and DCX. Increased numbers of Ki-67+ cells with a healthy, non-mature appearance were found in CA1-3. These were mainly due to glial and vasculature-associated changes, while DCX immunostaining appeared sensitive to postmortem breakdown. We found no indications for altered dentate gyrus neurogenesis. Our data obtained using validated methodology in a well-characterized, presenile cohort thus differ from previous data obtained in senile AD. They reflect clear differences in proliferative responsivity, particularly in the glia and vascular components, and suggest different underlying mechanisms in these groups.
Boekhoorn
Karin
K
Center for Neuroscience, Swammerdam Institute of Life Sciences, University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam, The Netherlands. boekhoorn@science.uva.nl
Joels
Marian
M
Lucassen
Paul J
PJ
D000368:Aged; D000544:Alzheimer Disease / Q000473:pathology*; D000963:Antimetabolites; D001808:Blood Vessels / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D001973:Bromodeoxyuridine; D049109:Cell Proliferation; D002560:Cerebrovascular Circulation; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006624:Hippocampus / Q000098:blood supply / Q000473:pathology* / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology; D009457:Neuroglia / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D014015:Tissue Banks
D000963:Antimetabolites; D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D001973:Bromodeoxyuridine