TY - JOUR
T1 - Prevention of Alzheimer's disease in high risk groups
T2 - Statin therapy in subjects with PSEN1 mutations or heterozygosity for apolipoprotein e epsilon 4
AU - Pollen, Daniel A.
AU - Baker, Stephen
AU - Hinerfeld, Douglas
AU - Swearer, Joan
AU - Evans, Barbara A.
AU - Evans, James E.
AU - Caselli, Richard
AU - Rogaeva, Ekaterina
AU - St George-Hyslop, Peter
AU - Moonis, Majaz
N1 - Funding Information:
We sincerely thank our subjects for their participation in these studies. We thank an anonymous foundation for initial support (DAP, MM). We also thank the families of Edith Marrone, Paul Riley and Peter Simmarano for arranging benefits to help support our work. This work was also supported by grants from the Ontario Research Fund (PGH) and Canadian Institutes of Health Research (ER, PGH). We are especially grateful to two anonymous reviewers whose constructive comments have greatly improved the present drafts.
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
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U2 - 10.1186/alzrt55
DO - 10.1186/alzrt55
M3 - Review article
C2 - 21062519
AN - SCOPUS:78149359327
SN - 1758-9193
VL - 2
JO - Alzheimer's Research and Therapy
JF - Alzheimer's Research and Therapy
IS - 5
M1 - 31
ER -