Alzheimer-type neuropathological changes in morbidly obese elderly individuals

Abstract

Middle age obesity increases risk for Alzheimer disease (AD). This study evaluated neuropathological changes in morbidly obese patients ranging in age from 21-70 years. 12 autopsied morbidly obese patients (> or = 136 kg, BMI 45.3-81.1, 7 male, 5 female, ages 21-70), without cognitive impairment, were compared to 10 non-obese controls (52-106 kg, BMI 17.4-32.5, 8 male, 2 female, ages 29-74), and 3 AD controls (1 male, 2 female, ages 63-78). Standard hippocampal sections were stained for Bielschowsky, A beta (4G8), tau (AT8), or A beta PP (monoclonal, Pierce) and evaluated using semiquantitative criteria. Obese patients had normal-sized brains, but larger hearts (713 +/- 273 vs. 438 +/- 71 g, p <0.01). Only rare brain lesions were noted in any patients < 65 years. Obese patients > 65 years showed high levels of all indices, in some cases comparable to those seen in AD. Compared to non-obese, non-AD controls, the differences in tau and A beta PP expression (but not A beta) were significant (p < 0.05, Mann-Whitney U-test). Alzheimer-type neuropathological changes were frequent in our small sample of morbidly obese elderly individuals without clinical history of cognitive impairment, approaching those seen in Alzheimer disease for some patients. Such changes were not seen in younger obese patients. These changes may be attributable to comorbid conditions such as congestive heart failure, obstructive sleep apnea, or metabolic lipid abnormalities.