Alzheimer's Disease: Pathophysiology, Hypotheses and Treatment Strategies

Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative disorder. One new case of AD is expected to be developed every 33 seconds. So, about million new cases will be developed per year and the total estimated prevalence is expected to reach 13.8 million by 2050 [1]. AD is characterized by a group of symptoms classified as cognitive and non-cognitive dysfunctions. The cognitive dysfunction includes memory loss, executive dysfunction and language difficulties while noncognitive dysfunction includes behavioral disturbances and psychiatric symptoms as hallucinations, delusion, agitation as well as depression [2]. In the late stage of the disease, cognitive performance of AD patients greatly declines to such an extent that they need complete support for all their daily activities [3, 4].

[1]  D. Van Dam,et al.  Neuropeptides in Alzheimer's disease: from pathophysiological mechanisms to therapeutic opportunities. , 2013, Current Alzheimer research.

[2]  A. Saunders.  Apolipoprotein E and Alzheimer Disease: An Update on Genetic and Functional Analyses , 2000, Journal of neuropathology and experimental neurology.

[3]  A. Ali,et al.  Comparative Study on the Influence of Epigallocatechin-3-gallat e and/or Coenzyme Q10 against Alzheimer's disease Induced by Aluminiumin Normally-Fed and Protein Malnourished Rats , 2016 .

[4]  A. Contestabile.  The history of the cholinergic hypothesis , 2011, Behavioural Brain Research.

[5]  B. Fredholm,et al.  Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. , 1999, Pharmacological reviews.

[6]  A. Hernández-Pinto,et al.  Somatostatin and Alzheimer's disease , 2008, Molecular and Cellular Endocrinology.

[7]  B. Strooper,et al.  Presenilin clinical mutations can affect γ‐secretase activity by different mechanisms , 2006, Journal of neurochemistry.

[8]  T. Wisniewski,et al.  Fibrillogenesis in Alzheimer's disease of amyloid beta peptides and apolipoprotein E. , 1995, The Biochemical journal.

[9]  J. Corwin,et al.  CSF somatostatin in Alzheimer's disease , 1984, Neurobiology of Aging.

[10]  C. Nemeroff,et al.  Corticotropin‐Releasing Factor (CRF), CRF‐Binding Protein (CRF‐BP), and CRF/CRF‐BP Complex in Alzheimer's Disease and Control Postmortem Human Brain , 1997, Journal of neurochemistry.

[11]  R. Cunha,et al.  Increase in the Number, G Protein Coupling, and Efficiency of Facilitatory Adenosine A2A Receptors in the Limbic Cortex, but not Striatum, of Aged Rats , 1999, Journal of neurochemistry.

[12]  A. Ali,et al.  The Potential Effect of Caffeine and Nicotine Co-administration againstAluminum-induced Alzheimer's disease in Rats , 2016 .

[13]  M. Higuchi,et al.  Somatostatin regulates brain amyloid β peptide Aβ42 through modulation of proteolytic degradation , 2005, Nature Medicine.

[14]  D. Selkoe,et al.  Translating cell biology into therapeutic advances in Alzheimer's disease , 1999, Nature.

[15]  M. Beal,et al.  Coenzyme Q10 decreases amyloid pathology and improves behavior in a transgenic mouse model of Alzheimer's disease. , 2011, Journal of Alzheimer's disease : JAD.

[16]  A. Ali,et al.  The Potential Effect of Epigallocatechin-3-Gallate alone or in Combination with Vitamin E and Selenium on Alzheimer’s Disease Induced by Aluminum in Rats , 2016 .

[17]  D. Selkoe.  Alzheimer's disease. , 2011, Cold Spring Harbor perspectives in biology.

[18]  B. Seltzer,et al.  Donepezil: an update , 2007, Expert opinion on pharmacotherapy.

[19]  L. Rajendran,et al.  Cellular basis of Alzheimer’s disease , 2010, Annals of Indian Academy of Neurology.

[20]  A. Burns,et al.  Psychiatric Phenomena in Alzheimer's Disease. I: Disorders of Thought Content , 1990, British Journal of Psychiatry.

[21]  M. Mattson,et al.  Overview of protein aggregation in single, double, and triple neurodegenerative brain amyloidoses , 2007, NeuroMolecular Medicine.

[22]  R. J. Kelleher,et al.  The presenilin hypothesis of Alzheimer's disease: Evidence for a loss-of-function pathogenic mechanism , 2007, Proceedings of the National Academy of Sciences.

[23]  D. Selkoe,et al.  Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics. , 2003, Annual review of pharmacology and toxicology.