Affiliations: [a] Oxford Project to Investigate Memory and Ageing (OPTIMA), Department of Pharmacology, University of Oxford, Oxford, UK
| [b] Department of Pharmacology, University of Oxford, Oxford, UK
| [c] Department of Physiology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt
| [d] Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London, UK
Correspondence:
[*]
Correspondence to: Dr. Michael J. Hurley, Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK. Tel.: +44 20 8016 8178; E-mail: [email protected].
Note: [1] Deceased 1 August 2019.
Abstract: Sporadic Alzheimer’s disease (AD) is a complex, multifactorial disease. We should therefore expect to find many factors involved in its causation. The known neuropathology seen at autopsy in patients dying with AD is not consistently seen in all patients with AD and is sometimes seen in patients without dementia. This suggests that patients follow different paths to AD, with different people having slightly different combinations of predisposing physical, chemical and biologic risk factors, and varying neuropathology. This review summarizes what is known of the biologic and chemical predisposing factors and features in AD. We postulate that, underlying the neuropathology of AD is a progressive failure of neurons, with advancing age or other morbidity, to rid themselves of entropy, i.e., the disordered state resulting from brain metabolism. Understanding the diverse causes of AD may allow the development of new therapies targeted at blocking the paths that lead to dementia in each subset of patients.
