Daniel D. Christensen, MD
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Objectives: To review the amyloid
hypothesis as the predominant mechanistic theory of
Alzheimer's disease and update the status of new
disease-modifying, anti-amyloid treatments in
clinical development.
Data Sources: Governmental Web sites
and those of professional Alzheimer's disease
associations and drug manufacturers were searched
for new drugs in development. An English-language search of PubMed (January 2003-January
2006) was conducted using the search terms
Alzheimer's disease and amyloid
hypothesis and each of the drugs and immunotherapies from the 4
identified classes of anti-amyloid, disease-modifying
therapies.
Study Selection and Data
Extraction: Studies and reports were selected on the basis of
recent publication, adequate methodology, and completeness of data.
Data Synthesis: Immunotherapy,
gamma-secretase inhibitors, selective neurotoxic
aggregated 42-amino acid peptide subspecies of amyloid beta
(Abeta42)-lowering agents
(tarenflurbil), inhibitors of amyloid aggregation
(tramiprosate), and statins show promise in clinical trials.
Safety remains an important factor.
Disease-modifying drugs that specifically target the amyloid
cascade and do not interact with essential biological
pathways are expected to possess a lower rate of
unintended adverse events.
Agents that selectively target
Abeta42 production (e.g., tarenflurbil), block Abeta
aggregation (e.g., tramiprosate), or enhance
alpha-secretase activity (statins) offer hope for disease
modification and prevention and do not appear to
interfere with other biological pathways.
Conclusions: Discovery of safe and
effective disease-modifying therapies will usher in a
new age of Alzheimer's disease treatment.
Prim Care Companion J Clin Psychiatry 2007;9(1):32-41
https://doi.org/10.4088/PCC.v09n0106
© Copyright 2007 Physicians Postgraduate Press, Inc.