Elevated luteinizing hormone expression colocalizes with neurons vulnerable to Alzheimer's disease pathology.
In individuals with Alzheimer's disease (AD), there is a two-fold elevation in the serum concentrations of the gonadotropins, luteinizing hormone (LH), and follicle stimulating hormone compared to age-matched controls. Whether this plays a role in disease pathogenesis is unclear. Nonetheless, gonadotropins are known to cross the blood brain barrier and the highest density of gonadotropin receptors in the brain are found within the hippocampus. We report for the first time the localization of LH in the cytoplasm of pyramidal neurons. In addition, we find a significant increase in LH in the cytoplasm of pyramidal neurons and neurofibrillary tangles of AD brain compared to age-matched control brain. Whereas the functional consequences of increased neuronal LH are unknown, it is notable that LH is primarily localized to those neurons that are known to be vulnerable to Alzheimer's disease-related neurodegeneration. Elevated serum and cortical neuron levels of LH, coupled with the decline in sex steroid production, could play important roles in the pathogenesis of AD.
Bowen
Richard L
RL
Voyager Pharmaceutical Corporation, Raleigh, North Carolina, USA.
Smith
Mark A
MA
Harris
Peggy L R
PL
Kubat
Zvezdana
Z
Martins
Ralph N
RN
Castellani
Rudolph J
RJ
Perry
George
G
Atwood
Craig S
CS
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D015984:Causality; D004967:Estrogens / Q000378:metabolism; D005246:Feedback / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D007986:Luteinizing Hormone / Q000097:blood*; D008297:Male; D008875:Middle Aged; D017966:Pyramidal Cells / Q000378:metabolism* / Q000473:pathology; D011974:Receptors, LH / Q000378:metabolism; D012727:Sex Characteristics; D013739:Testosterone / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*
D004967:Estrogens; D011974:Receptors, LH; D013739:Testosterone; D007986:Luteinizing Hormone