RECENT ADVANCES IN ALZHEIMER'S DISEASE: CAUSES AND TREATMENT Review Article KIRANJIT KAUR*, RAJNEET KAUR, MANJINDER KAUR G. H. G. Khalsa College of Pharmacy, Gurusar Sadhar, Ludhiana (India) 141104 Email: rajneet.manchanda@gmail.com Received: 27 Aug 2015 Revised and Accepted: 19 Dec 2015 ABSTRACT Alzheimer’s disease (AD) is a destructive neurodegenerative disorder characterized by progressive memory defeat and impairment in behavior, language, and visuospatial skills. Neuropsychiatric symptoms such as apathy, depression, aggression, agitation, sleep disruption, and psychosis are now recognized as core symptoms of AD that are expressed to varying degrees throughout the course of disease. The neuro pathological features of AD comprise extracellular senile plaques constituted of β-amyloid (Aβ) pledges, intracellular neurofibrillary tangles (NFTs), and cerebral atrophy; others include apolipoprotein E, oxidative stress, mitochondrial dysfunction and cholinergic hypothesis. Anti-amyloid therapy is available for the treatment of Alzheimer’s disease, others are anticholinergic therapy, and therapy for mitochondrial dysfunction, γ-secretase inhibitors (GSI) and modulators (GSM), -secretase (BACE1) inhibitors, Glial modulating drugs includes RAGE receptor antagonists, TNF-α antagonists, neuroprotective drugs such as antioxidants, phosphodiesterase inhibitors, PPARγ agonists, and anti-tau or tau modulators like microtubule stabilizers, kinase inhibitors. This review includes discussion on neurobiological mechanisms and newly developed compounds which have lesser side effects and are proving more efficient for treatment of Alzheimer’s disease. Keywords: Alzheimer's disease, Alzheimer causes and treatment © 2016 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) INTRODUCTION Alzheimer’s disease (AD) is a critical neurodegenerative illness characterized by memory loss and diminished performance, language, and visuospatial skills [1]. Epidemiological data show that the occurrence of AD increases with age and doubles every 5 y after 65 y of age [2, 3]. There were about 26.6 million cases of AD in the world in 2006 and it is predictable that the worldwide dominance of AD will grow fourfold to 106.8 million by the year 2050 [4]. The neuropathological features of AD involve extracellular senile plaques constituted of β-amyloid (Aβ) pledges, intracellular neurofibrillary tangles (NFTs), and cerebral atrophy [5]. Aβ, produced from the proteolytic administration of amyloid precursor protein (APP), has been projected to have a causative role in the generation of AD and this Accumulated Amyloid-β can provoke euro-toxicity by generating oxidative stress and inflammation in the brain [6, 7]. Causative factors Both non-modifiable and modifiable risk factors are involved in AD. Non-modifiable factors include age which is one of the important risk factors, genes, family history, Down’s syndrome while modifiable factors include cognitive engagement, diet/nutritional supplement intake, physical activity level, type 2 diabetes, alcohol consumption, mood disorders, hypertension, hypercholesterolemia, and smoking [8-11]. Genetic factors Alzheimer’s disease happens in both familial and an irregular form, also recognized as early onset or late onset Alzheimer's disease (LOAD), respectively [12]. Early-onset domestic AD is generally produced by autosomal dominant variations in the genes for amyloid precursor protein (APP), presenilin 1 and presenilin 2. This form of AD accounts for around 2–5% of all AD cases [13]. The apoE4 allele is the single verified heritable factor in the progress of together the early and late-onset practices of AD. This factor rises vulnerability to AD however it is neither essential nor adequate for the progress of this disease. In late-onset irregular form, greater the number of the apoE4 alleles, the greater the possibility of AD and the lesser the age of onset. The risk influence of the occurrence of the apoE4 allele declines with age. Usually, around 15-20% of AD cases could be recognized to this risk [14]. Vascular factors Smoking Smoking is a well-recognised cardiac risk factor and facilitates oxidative stress, inflammation and atherosclerosis which are identified as the risk factors for neurodegeneration [15]. Oxidative stress promotes augmented β-secretase cleavage of APP and abnormal tau phosphorylation. It may openly enable the amyloidogenic pathway involved in Aβ oligomer invention and extracellular fibrillar Aβ aggregation, as well as abnormal tau phosphorylation [16]. Alcohol It is well predictable that alcohol abuse causes alcohol dementia. In heavy consumers, alcohol causes injuries in the brain. Light to adequate alcohol intake is found to be closely associated with brain atrophy and volume loss [17, 18]. Obesity It has been showed that being obese contributes to dementia and cerebral decay. Obesity leads to dementia, cerebral damage and consistent neurological modifications [19]. Blood pressure and management of hypertension High blood pressure is one of the most significant manageable risk factors for stroke, which in turn can result in vascular dementia. It has been reported that there is a close relationship between AD and hypertension [20]. It has been recently proved that antihypertensive drugs have a protective effect against the progress of dementia and AD [21-23]. The antihypertensive remedy may protect against dementia and AD by decaying the atherosclerotic process, reducing the number of atherosclerotic scratches and improving cerebral perfusion [24]. Diabetes mellitus It has been reported that there is an increased risk of vascular dementia in persons with diabetes [25-27]. Binding of insulin or IGF- 1 causes a conformational variation of the receptor leading to their autophosphorylation on definite tyrosine residues on the β-subunit resulting in activation of the insulin receptor substrate-1 (IRS-1) [28, 29]. The latter, in turn, stimulates two main signaling pathways: initially the PI3K pathway, which is involved in the preservation of International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 8, Issue 2, 2016