Sporadic Alzheimer disease (AD) is caused in part by decreased clearance of the β-amyloid
(Aβ) peptide breakdown products. Lipid-depleted (LD) apolipoproteins are less effective at
binding and clearing Aβ, and LD Aβ peptides are more toxic to neurons. However, not much
is known about the lipid states of these proteins in human cerebrospinal fluid.
To characterize the lipidation states of Aβ peptides and apolipoprotein E in the
cerebrospinal fluid in adults with respect to cognitive diagnosis and APOE ε4
allele carrier status and after a dietary intervention.
Randomized clinical trial.
Veterans Affairs Medical Center clinical research unit.
Twenty older adults with normal cognition (mean [SD] age, 69  years) and 27 with amnestic mild
cognitive impairment (67  years).
Randomization to a diet high in saturated fat content and with a high glycemic index (High diet;
45% of energy from fat [>25% saturated fat], 35%-40% from carbohydrates with a mean glycemic
index >70, and 15%-20% from protein) or a diet low in saturated fat content and with a low
glycemic index (Low diet; 25% of energy from fat [<7% saturated fat], 55%-60% from carbohydrates
with a mean glycemic index <55, and 15%-20% from protein).
Main Outcomes and Measures
Lipid-depleted Aβ42 and Aβ40 and apolipoprotein E in cerebrospinal fluid.
Baseline levels of LD Aβ were greater for adults with mild cognitive impairment compared
with adults with normal cognition (LD Aβ42, P = .05; LD Aβ40,
P = .01). These findings were magnified in adults with mild cognitive
impairment and the ε4 allele, who had higher LD apolipoprotein E levels irrespective of
cognitive diagnosis (P < .001). The Low diet tended to decrease LD
Aβ levels, whereas the High diet increased these fractions (LD Aβ42,
P = .01; LD Aβ40, P = .15). Changes
in LD Aβ levels with the Low diet negatively correlated with changes in cerebrospinal fluid
levels of insulin (LD Aβ42 and insulin, r = −0.68
[P = .01]; LD Aβ40 and insulin,
r = −0.78 [P = .002]).
Conclusions and Relevance
The lipidation states of apolipoproteins and Aβ peptides in the brain differ depending on
APOE genotype and cognitive diagnosis. Concentrations can be modulated by diet.
These findings may provide insight into the mechanisms through which apolipoprotein E4 and unhealthy
diets impart risk for developing AD.