Phosphate/calcium alterations in the first stages of Alzheimer's disease: implications for etiology and pathogenesis.
The present study tested aspects of a novel etiological/pathogenetic hypothesis of Alzheimer's disease (AD), which proposes that alterations in endocrine regulation of peripheral calcium/phosphate (Ca/PO4) homeostasis (e.g., by glucocorticoids, vitamin D, etc.) induce and/or reflect altered calcium homeostasis and neurotoxicity in brain neurons. Two key predictions of this hypothesis were tested, namely that: (1) alterations in serum Ca and/or PO4 regulation should be present before or near the onset of AD and (2) these alterations should be found consistently in subjects with unconfounded AD. Previous studies have sought evidence of changes in Ca regulation primarily late in the disease, and usually in severely demented, thin and immobile inpatients in whom Ca/PO4 measures are likely to be confounded. In the present study, only mobile, relatively healthy, adequately nourished outpatients with probable AD were selected. In comparison to age-matched controls or demented subjects with even mild indications of vascular contributions, the AD subjects were characterized by lower serum PO4 and, to a lesser degree, lower serum Ca as well as a higher chloride/PO4 ratio. On serum chemistry tests from the first stages of AD (within 1 or 3 years after the onset of cognitive symptoms), these changes in serum PO4/Ca were as pronounced as they were later in the disease. Moderately low values of either PO4, Ca, or both (below -1.0 S.D. from the control group mean) identified 74% of all AD subjects and 100% of early onset AD subjects, in comparison to only 46% of mixed/vascular dementia subjects and 31% of normal age-matched controls. Thus, the results were consistent with the predictions and may have significant etiological/pathogenetic implications. If larger tests confirm these frequencies, serum Ca/PO4 indices may also prove useful in differential diagnosis.
Landfield
P W
PW
Department of Pharmacology, University of Kentucky College of Medicine, Lexington 40536.
Applegate
M D
MD
Schmitzer-Osborne
S E
SE
Naylor
C E
CE
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D002118:Calcium / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D010710:Phosphates / Q000097:blood*
D001786:Blood Glucose; D010710:Phosphates; D002784:Cholesterol; D002118:Calcium