Prevention of Alzheimer's disease in high risk groups: Statin therapy in subjects with PSEN1 mutations or heterozygosity for apolipoprotein e epsilon 4

Daniel A. Pollen, Stephen Baker, Douglas Hinerfeld, Joan Swearer, Barbara A. Evans, James E. Evans, Richard John Caselli, Ekaterina Rogaeva, Peter St George-Hyslop, Majaz Moonis

Research output: Contribution to journalArticle

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Abstract

Because cerebrospinal fl uid (CSF) abnormalities in presymptomatic subjects with PSEN1 (presenilin 1) mutations may be observed 4 to 12 years prior to the estimated age at onset, it is possible to test putative therapies on the CSF analytes that correlate with neurodegeneration during this presymptomatic window of clinical opportunity. It is also possible to test the same therapy on a comparison group with increased risk status conferred by both hyperlipidemia and heterozygosity for apolipoprotein Eε4. To our knowledge, the only putative therapy thus far tested in such a common design has been statin therapy. The results of these tests show increases in soluble amyloid precursor protein (sAPP)a correlating with statininduced decreases in serum cholesterol levels in the non-PSEN1 subjects. This result could be one functional correlate for part of the substantial risk reduction for late onset Alzheimers disease recently reported in the Rotterdam study, a large, long-term prospective statin trial. Statin therapy signifi cantly decreased both sAPPa and sAPPa in presymptomatic PSEN1 subjects. Initially, elevated phospho-tau levels in PSEN1 subjects did not further increase during the 2 to 3 years of statin therapy, possibly indicative of a prophylactic effect. These results suggest that large and longer term trials of statin therapy correlating changes in CSF biomarker levels with clinical course may be warranted in both presymptomatic PSEN1 and non-PSEN1 subjects.

Original languageEnglish (US)
Article number31
JournalAlzheimer's Research and Therapy
Volume2
Issue number5
DOIs
StatePublished - 2010

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Presenilin-1
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Apolipoproteins
Group Psychotherapy
Alzheimer Disease
Mutation
Therapeutics
Apolipoprotein E4
Amyloid beta-Protein Precursor
Risk Reduction Behavior
Hyperlipidemias
Age of Onset
Biomarkers
Cholesterol
Serum

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology
  • Cognitive Neuroscience

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Prevention of Alzheimer's disease in high risk groups : Statin therapy in subjects with PSEN1 mutations or heterozygosity for apolipoprotein e epsilon 4. / Pollen, Daniel A.; Baker, Stephen; Hinerfeld, Douglas; Swearer, Joan; Evans, Barbara A.; Evans, James E.; Caselli, Richard John; Rogaeva, Ekaterina; St George-Hyslop, Peter; Moonis, Majaz.

In: Alzheimer's Research and Therapy, Vol. 2, No. 5, 31, 2010.

Research output: Contribution to journalArticle

Pollen, Daniel A. ; Baker, Stephen ; Hinerfeld, Douglas ; Swearer, Joan ; Evans, Barbara A. ; Evans, James E. ; Caselli, Richard John ; Rogaeva, Ekaterina ; St George-Hyslop, Peter ; Moonis, Majaz. / Prevention of Alzheimer's disease in high risk groups : Statin therapy in subjects with PSEN1 mutations or heterozygosity for apolipoprotein e epsilon 4. In: Alzheimer's Research and Therapy. 2010 ; Vol. 2, No. 5.
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