Emerging drug targets for Aβ and tau in Alzheimer's disease: a systematic review.
OBJECTIVE
Currently, treatment for Alzheimer's disease (AD) focuses on the cholinergic hypothesis and provides limited symptomatic effects. Research currently focuses on other factors that are thought to contribute to AD development such as tau proteins and Aβ deposits, and how modification of the associated pathology affects outcomes in patients. This systematic review summarizes and appraises the evidence for the emerging drugs affecting Aβ and tau pathology in AD.


METHODS
A comprehensive, systematic online database search was conducted using the databases ScienceDirect and PubMed to include original research articles. A systematic review was conducted following a minimum set of standards, as outlined by The PRISMA Group . Specific inclusion and exclusion criteria were followed and studies fitting the criteria were selected. No human trials were included in this review. In vitro and in vivo AD models were used to assess efficacy to ensure studied agents were emerging targets without large bodies of evidence.


RESULTS
The majority of studies showed statistically significant improvement (P < 0.05) of Aβ and/or tau pathology, or cognitive effects. Many studies conducted in AD animal models have shown a reduction in Aβ peptide burden and a reduction in tau phosphorylation post-intervention. This has the potential to reduce plaque formation and neuronal degeneration.


CONCLUSIONS
There are many emerging targets showing promising results in the effort to modify the pathological effects associated with AD. Many of the trials also provided evidence of the clinical effects of such drugs reducing pathological outcomes, which was often demonstrated as an improvement of cognition.
Sunderland Pharmacy School, Department of Pharmacy, Health and Wellbeing, The University of Sunderland, City Campus, Chester Road, Sunderland, SR1 3SD, United Kingdom.
Sophie
S
West
Sunderland Pharmacy School, Department of Pharmacy, Health and Wellbeing, The University of Sunderland, City Campus, Chester Road, Sunderland, SR1 3SD, United Kingdom.
Praveen
P
Bhugra
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002986:Clinical Trials as Topic; D003071:Cognition / Q000187:drug effects; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D006801:Humans; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D016875:tau Proteins
Alzheimer's disease; Aβ; emerging targets; systematic review; tau