Abnormal lipid metabolism contributes to a higher risk of neuritic plaque formation, but not presence of neurofibrillary tangles.
High levels of total cholesterol (TC), LDL cholesterol (LDLC), TC/HDL cholesterol (HDLC), and non-HDLC cholesterol were associated with plaque-type Alzheimer’s disease pathology, according to the results of a study appearing in the September 13 Neurology.
“We searched for evidence of Alzheimer’s disease–related pathologic risk of abnormal lipid metabolism,” the investigators, led by Takashi Matsuzaki, MD, PhD, from the Graduate School of Medical Sciences at Kyushu University in Fukuoka, Japan, wrote. “Our study clearly makes the point that lipid profiles may contribute directly or indirectly to plaque burden in the brain.”
To clarify the relationship between abnormal lipid metabolism and Alzheimer’s disease, Dr. Matsuzaki and colleagues examined 147 autopsy brain samples from people who had undergone cholesterol testing 10 to 15 years prior.
None of the 147 participants showed signs of dementia at initial testing, but 50 (34%) developed dementia before death; 26 of these cases were specifically Alzheimer’s-type dementia. The majority of the samples had at least some presence of neurofibrillary tangles (127) and neuritic plaque formation (100).
Dyslipidemia May Be a Risk Factor for Neuritic Plaque Formation
Dr. Matsuzaki’s group then compared lipid profile values with presence of neuritic plaques or neurofibrillary tangles. “Unfavorable lipid metabolism was significantly associated with plaque-type Alzheimer’s disease pathology even in sparse to moderate stages,” the investigators noted. “The subjects with neuritic plaques showed significantly higher TC, LDLC, TC/HDLC, LDLC/HDLC, and non-HDLC levels compared to subjects without neuritic plaques.” This association remained significant after adjustment for age, sex, glucose level, blood pressure, BMI, and lifestyle factors.
When the investigators conducted a separate analysis comparing the risk of neuritic plaques among quartiles of each lipid profile, they found that “the subjects in the highest quartiles of these lipid profiles had significantly higher risks of neuritic plaques compared to subjects in the lower respective quartiles, which may suggest a threshold effect.” The researchers noted that further studies with larger sample sizes are needed to determine exact threshold levels.
“Neurofibrillary tangle pathology was less associated with disturbed lipid metabolism than was the formation of neuritic plaques,” the researchers stated, adding that this dissociation suggests that plaques and neurofibrillary tangles are driven by very different factors.
“The results of this study suggest that dyslipidemia increases the risk of plaque-type pathology … however, dyslipidemia might also affect mechanisms other than neuritic plaque formation in the onset of dementia or Alzheimer’s disease,” the investigators concluded. “Further studies are required to determine if there is a causal link between dyslipidemia and the development of neuritic plaques or other Alzheimer’s disease-related pathology. In the future, adequate control of cholesterol, in addition to the control of diabetes, might contribute to a strategy for the prevention of Alzheimer’s disease.”
—Ariel Jones