{"id":2962,"date":"2018-12-23T15:21:21","date_gmt":"2018-12-23T15:21:21","guid":{"rendered":"https:\/\/www.mybiosource.com\/learn\/?p=2962"},"modified":"2024-04-04T08:03:43","modified_gmt":"2024-04-04T08:03:43","slug":"an-insight-into-alzheimers","status":"publish","type":"post","link":"https:\/\/www.mybiosource.com\/learn\/an-insight-into-alzheimers\/","title":{"rendered":"An Insight into Alzheimer’s"},"content":{"rendered":"\n\n\n
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Table of Contents<\/u><\/strong><\/h3>\n

I. Introduction<\/strong><\/a>
\n\u2022 Background of Alzheimer’s disease (AD)
\n\u2022 Prevalence of AD
\nII. Pathophysiology of AD<\/strong><\/a>
\n\u2022 Definition of dementia
\n\u2022 Early symptoms of AD
\n\u2022 Brain changes associated with AD
\n\u2022 Beta-amyloid plaques
\n\u2022 Tau tangles
\n\u2022 Microglia activation
\nIII. Treatment strategies for AD<\/strong><\/a>
\n\u2022 Current treatments: AChEIs and NMDA receptor antagonists
\n\u2022 Limitations of current treatments
\n\u2022 Disease-modifying therapies
\nIV. Conclusion<\/strong><\/a><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Alois Alzheimer<\/span> first described Alzheimer\u2019s disease<\/span> in 1906 at a conference in Tubingen, Germany. Since its first documentation, many aspects of AD<\/span> pathophysiology have been discovered and understood, however, gaps of knowledge continue to exist. Alzheimer\u2019s disease (AD) is a degenerative brain disease and the most common cause of dementia<\/span>.<\/p>\n

Dementia affects the memory, thinking process, orientation, comprehension, calculation, learning ability, language, and judgment. Research suggests that AD-associated brain changes start long before symptoms appear. Initially, brain compensates for the changes, enabling individuals to continue to function normally. With significant neuronal damage, the brain becomes unable to compensate for the changes and individuals show subtle cognitive<\/span> decline followed by memory loss or confusion as to time or place. Later still, basic bodily functions such as swallowing are impaired. Approximately 200,000 people younger than 65 years with AD comprise the younger-onset AD population; 5 million are age 65 years or older. It is expected that by 2050, one new case of AD is expected to develop every 33 s, or nearly a million new cases per year, and the total estimated prevalence is expected to be 13.8 million. Several hypotheses have been put forward to explain this multifactorial disorder. <\/strong>However, to understand the disease it\u2019s important to understand the brain changes which are associated with AD. A healthy adult brain has about 100 billion neurons<\/span>, and their connection point with other neurons are called synapses which are 100 trillion in number. Information flows in tiny bursts of chemicals that are released by one neuron and detected by a receiving neuron. Synapses allow signals to travel rapidly through the brain\u2019s neuronal circuits. They create the cellular basis of memories, thoughts, sensations, emotions, movements and, skills. The two changes in the brain which have been recorded in AD are (called beta-amyloid<\/span> plaques) and protein tau<\/span> (called tau tangles). Beta-amyloid, which is a protein fragment gets accumulated outside neurons and an abnormal form of tau protein accumulates inside the neurons. The neuron-to-neuron communication at synapses is interfered because of beta-amyloid plaques leading to cell death. While tau tangles block the transport of nutrients and other essential molecules inside neurons. Due to the presence of toxic beta-amyloid and tau proteins, immune system cells in the brain called microglia<\/span> gets activated. Microglia<\/span> try to clear the toxic proteins and when it can\u2019t keep up with the cleaning process it leads to chronic inflammation. AD being a progressive disease early intervention would offer the best chance of slowing the progression. Earlier beginning of AD was defined by dementia symptoms and confirmation was only possible by estimating levels of beta-amyloid and tau in the autopsy brain. However, due to the development of biomarkers, revised diagnostic guidelines were published by the National Institute on Aging<\/span> (NIA) and the Alzheimer\u2019s Association<\/span> in 2011. Beta-amyloid PET<\/span> imaging accurately reflects levels of amyloid deposits (called neuritic plaques) in the brain. While elevated levels of beta-amyloid detected via PET cannot be used in clinical practice to conclusively diagnose the disease, they give clinicians reason to conduct additional Alzheimer\u2019s testing. To aid in the diagnosis of AD three amyloid PET radiotracers florbetapir<\/span>, flutemetamol and florbetaben are currently approved by U.S. FDA. Elevated cortical tau shown with PET imaging is a biomarker for neurofibrillary tangles. FDG-PET imaging showing reduced glucose metabolism and structural MRI<\/span> showing atrophy are biomarkers for neurodegeneration<\/span>. Few promising neuroimaging biomarkers along with CSF\/Blood biomarker are under investigation. In 2016 Jack et al proposed a descriptive classification for patients based on the presence or absence of three key factors: A\u03b2 (A), NFTs (T), and neurodegeneration (N), to be complemented by cognitive<\/span> evaluation. The A\/T\/N classification system is not an individual diagnostic tool, but rather a biomarker classification scheme that allows the description and characterization of a wide range of patients, based on specific biomarkers.<\/p>\n

The currently available treatment strategies include AChEIs (acetylcholinesterase inhibitor) and NMDA (N-methyl D-aspartate) receptor antagonists. Though many drugs are under trial only four drugs donepezil<\/span>, galantamine<\/span>, rivastigmine<\/span> and memantine<\/span> are currently approved for the treatment of AD. First three drugs act on central nervous system<\/span> (CNS) cholinergic pathways and have anticholinesterase activity. Galantamine<\/span>, a natural-product alkaloid is also active as an allosteric modulator at nicotinic acetylcholine<\/span> receptors<\/span>. Memantine<\/span> is the recently approved drug and targets the N-methyl-D-aspartate<\/span> (NMDA) receptor and glutaminergic pathways that target symptoms at its best. Early clinical trials for approved AD drugs are insufficient to provide useful guidelines for clinical practice. Safety and efficacy of the drugs in the long-term (for example, greater than six months) are not clear and they contribute least in modifying the primary pathological processes involved in AD. However, the drugs provide symptomatic relief and are generally administered as palliative therapy with the aim of slowing the decline in quality of life. In order to modify the disease process novel strategies have been developed. The major target is Ab and tau-based therapeutics, which is a major key to unlock this disease in the near future. Disease-modifying therapies demand complete knowledge about the various metabolic pathways<\/span> which includes the production of Ab from APP, in vivo<\/span> clearance and pathophysiological events that lead to fibril formation and deposition into plaque<\/span>.<\/p>\n

Despite the immense knowledge regarding this complex and multifactorial disease, there is a dearth of disease management options. Currently available drugs for the treatment, unfortunately, target symptoms only. New discoveries contributing to the elucidation of the molecular pathogenesis of AD and its relations are crucial. Also, the development of new therapeutic strategies which act at the root level of the disease is the need of the hour, where current drug therapy lacks the ability to prevent occurrence and progression of AD.<\/p>\n

References<\/p>\n

    \n
  1. Wilson RS, Segawa E, Boyle, PA, Anagnos SE, Hizel LP, Bennett DA. The natural history of cognitive<\/span> decline in Alzheimer\u2019s disease. Psychol Aging 2012;27(4):1008-17.<\/li>\n
  2. Alzheimer\u2019s Association<\/span>. Alzheimer\u2019s disease facts and figures. Alzheimers Dementia 2014;10(2):47\u201392.<\/li>\n
  3. Kumar A, Dogra S. Neuropathology and therapeutic management of Alzheimer\u2019s disease \u2013 an update. Drugs Future 2008;33(5):433\u201346.<\/li>\n
  4. National Institutes of Health<\/span>. National Institute on Aging. What Happens to the Brain in Alzheimer\u2019s Disease? Available at https:\/\/www.nia.nih.gov\/health\/what-happens-brainalzheimers-disease. Accessed October 10, 2017.<\/li>\n
  5. Jack CR Jr., Bennett DA, Blennow K, et al. 2016. A\/T\/N: an unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology<\/span> 87:539\u201347.<\/li>\n
  6. Auld DS, Kornecook TJ, Bastianetto S, Quirion R. Alzheimer\u2019s disease and the basal forebrain<\/span> cholinergic system: relations to b-amyloid peptides, cognition, and treatment strategies. Prog Neurobiol 2002;68(3):209\u201345.<\/li>\n
  7. Winblad B, Poritis N. 1999. Memantine in severe dementia: results of the 9M-Best Study (benefit and efficacy in severely demented patients during treatment with memantine). Int. J. Geriatr. Psychiatry 14:135\u201346 3.<\/li>\n
  8. Pereira AC, Lambert HK, Grossman YS, et al. 2014. Glutamatergic regulation prevents hippocampaldependent age-related cognitive<\/span> decline through dendritic spine clustering. PNAS 111:18733\u201338<\/li>\n
  9. Kurz A, Perneczky R. Novel insights for the treatment of Alzheimer\u2019s disease. Prog Neuropsychopharmacol Biol Psychiatry 2011;35(2):373\u20139.<\/li>\n<\/ol>\n

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    Table of Contents I. Introduction \u2022 Background of Alzheimer’s disease (AD) \u2022 Prevalence of AD II. Pathophysiology of AD \u2022 Definition of dementia \u2022 Early symptoms of AD \u2022 Brain changes associated with AD \u2022 Beta-amyloid plaques \u2022 Tau tangles \u2022 Microglia activation III. Treatment strategies for AD \u2022 Current treatments: AChEIs and NMDA receptor […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"off","_et_pb_old_content":"","_et_gb_content_width":"","footnotes":""},"categories":[1],"tags":[80],"class_list":["post-2962","post","type-post","status-publish","format-standard","hentry","category-uncategorized","tag-alzheimers"],"_links":{"self":[{"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/posts\/2962","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/comments?post=2962"}],"version-history":[{"count":3,"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/posts\/2962\/revisions"}],"predecessor-version":[{"id":9282,"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/posts\/2962\/revisions\/9282"}],"wp:attachment":[{"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/media?parent=2962"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/categories?post=2962"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.mybiosource.com\/learn\/wp-json\/wp\/v2\/tags?post=2962"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}