Nanomedicine and Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive and fatal neurological disorder causing cognitive and behavioural impairments. It affects over 35 million people worldwide and one in nine over the age of 69 alone [1]. Despite being first described in 1906 by Dr. Alois Alzheimer and considerable research efforts made, promising diagnosis and therapy approaches are very slow in progress.

The disease is still not fully understood yet commonly accepted hallmarks of AD pathology are the accumulation of amyloid plaques and neurofibrillary tangles leading to progressive neurodegeneration. Current symptomatic therapy approaches (ie. Acetylcholinesterase inhibitors, tacrine, memantine) have several limitations such as side effects, half-life limitations and poor pharmacokinetic parameters. Additionally, early stage markers and appropriate diagnostic tools are still lacking.

Nanomedicine bears promising new approaches for AD treatment and diagnostics, including drug delivery systems, neuroregeneration and neuroprotection strategies.

The most straightforward option is the delivery of AD drugs using nanoparticles. These need to be able to cross the blood-brain barrier (BBB) and reach pharmacologically relevant levels. Nano-mediated drug delivery approaches for tacrine and rivastigmine have delivered promising results in the recent years using different routes of delivery and different nano- carrier systems. A summary of different nano-carrier systems used was published by Fonseca-Santos et al. 2015 [2].

Early diagnosis of AD is crucial for immediate treatment and ideally prevention of neurodegeneration. Neurodegeneration can already occur long before AD symptoms appear. Hence the underlying AD pathology has to be detected as early as possible. Areas in diagnosis mainly used currently are clinical assessments, neuroimaging, neuropsychological testing and the detection of CSF biomarkers (i.e. tau protein, Aβ42, amyloid-β-derived diffusible ligands) [3]. Nanomedicine based approaches bear great potential due to a very high detection sensitivity, hence independence of disease severity. An ultrasensitive bio- barcode assay has been developed and successfully used for the detection of amyloid-β- derived diffusible ligands (ADDLs). The use of engineered gold nanoparticles in this novel assay provides detection of biomarker concentrations at much lower concentrations than an ELISA assay [4].

AD is a global burden with a complex pathology requiring interdisciplinary research efforts in the search of promising therapeutic and diagnostic approaches. Nanotechnology is a new ally in the field yet certainly one that has already shown great potential and will continue to do so.

[1] Alzheimer’s Disease International, World Alzheimer Report 2015: The Global Impact of Dementia, October 2015

[2] Int J Nanomedicine, Nanotechnology-based drug delivery systems for the treatment of Alzheimer’s disease, August 2015

[3] J Alzheimers Dis, Nanotechnology solutions for Alzheimer’s disease: advances in research tools, diagnostic methods and therapeutic agents, March 2008

[4] Proc Natl Acad Sci U S A, Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer’s disease

Fellow’s Name: Anne Iltzsche
Partner Institution: Kings College London
E-mail address: anne.iltzsche@kcl.ac.uk

Posted in Fellows Updates