Plasma levels of beta-amyloid(1-40), beta-amyloid(1-42), and total beta-amyloid remain unaffected in adult patients with hypercholesterolemia after treatment with statins.
BACKGROUND
Epidemiological studies suggest that statins reduce the risk of developing Alzheimer disease. Cell and animal experiments have revealed a connection between cholesterol metabolism and the processing of amyloid precursor protein. To our knowledge, the mechanism for statins in risk reduction of Alzheimer disease is unknown.


OBJECTIVE
To test the effect of statin treatment on beta-amyloid (A beta) metabolism in humans.


METHODS
A prospective, randomized, dose-finding 36-week treatment trial with statins. Plasma samples were taken at baseline (week 0) and at weeks 6, 12, and 36.


METHODS
Outpatient clinical study at a university hospital.


METHODS
Thirty-nine patients who met the criteria for hypercholesterolemia.


METHODS
Patients were randomized to oral treatment with either simvastatin or atorvastatin calcium according to the following regimen: simvastatin, 40 mg/d, or atorvastatin, 20 mg/d, for 6 weeks; followed by simvastatin, 80 mg/d, or atorvastatin, 40 mg/d, for 6 weeks; and finally, simvastatin, 80 mg/d, or atorvastatin, 80 mg/d, for 24 weeks.


METHODS
Plasma levels of A beta(1-40) and A beta(1-42) were measured using 2 enzyme-linked immunosorbent assays, and total A beta was quantified by Western blotting.


RESULTS
Treatment with both statins reduced total plasma cholesterol levels by 56% (P =.00). The plasma levels of A beta(1-40), A beta(1-42), and total A beta were stable in individual patients during the treatment period. No significant change in the level of A beta(1-40), A beta(1-42), or total A beta was found.


CONCLUSIONS
This study questions the effect of statins on the processing of amyloid precursor protein in humans.
Höglund
Kina
K
Institute of Clinical Neuroscience, The Sahlgrenska Academy at Göteborg, Sweden. kina.hoglund@neuro.gu.se
Wiklund
Olov
O
Vanderstichele
Hugo
H
Eikenberg
Oliver
O
Vanmechelen
Eugeen
E
Blennow
Kaj
K
D000328:Adult; D000368:Aged; D016229:Amyloid beta-Peptides / Q000097:blood*; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D019821:Simvastatin / Q000627:therapeutic use*; D013997:Time Factors
D016229:Amyloid beta-Peptides; D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D008055:Lipids; D010446:Peptide Fragments; D011758:Pyrroles; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D000069059:Atorvastatin; D019821:Simvastatin