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Overview of Overview of Alzheimer's Disease

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Alzheimer’s disease (AD) is the most common form of dementia and the sixth leading cause of death in the United States1.  Dementia is defined as the loss of memory and other mental abilities severe enough to interfere with daily life.  In AD, patients suffer from progressive and irreversible loss of cognitive function, such as thinking, remembering and reasoning, until they ultimately lose the ability to carry out simple tasks or take care of themselves1,2,3

There are two forms of AD: sporadic or late-onset AD and familial or early-onset AD.  Familial AD arises through the malfunction of three genes, APP, PSEN-1 and -2, and is an inheritable form of AD3. Over 95% of AD cases are late-onset in which the cause is relatively unknown.  Although, the cause likely includes a combination of genetic, environmental and lifestyle factors which may differ from person to person1.   

Alzheimer’s disease is named after Dr. Alois Alzheimer, who, in 1906 noted changes in the brain tissue of a woman who died of a previously unseen mental illness with symptoms including memory loss, language problems and unpredictable behavior.  Upon examination of her brain, he found abnormal clumps (amyloid plaques) and tangled fibers (neurofibrillary tangles)1.  These amyloid plaques and neurofibrillary tangles are still considered hallmarks of AD pathology.

The pathology of AD begins decades before any symptomatic manifestation. The pathology is multifactorial, involving extracellular amyloid (Aβ) plaques, intracellular neurofibrillary tangles containing hyperphosphorylated tau, a large amount of neuroinflammation and oxidative stress, with all of this together resulting in loss of synaptic connections, neuronal death and brain atrophy.  The outcome is the clinical manifestations of symptoms and this is part of the reason the disease is so hard to treat.  The initial insult to the brain happens 10-15 years prior to clinical diagnosis of AD4.        

It is generally accepted that deposition of Aβ peptide in the brain is the primary event in AD pathology.  The Aβ peptide is generated by sequential and improper cleavage of the Amyloid Precursor Protein (APP).  Once the level of peptide reaches detectable levels, the peptides become insoluble, misfolds and accumulates into Aβ plaques4.  On the other hand, neurofibrillary tangles are formed by abnormally hyperphosphorylated tau protein.  Normal tau protein binds and stabilizes micortubules in neurons and also supports axonal transport.  When tau becomes hyperphosphorylated it aggregates and causes microtubule instability and transport failure, ultimately leading to cell death.  All of this disruption within the brain triggers a large neuroinflammatory response and increases oxidative stress within the brain. Scientists continue to unravel the complex pathologies and brain changes involved in the onset and progression of this debilitating disease.       

Currently there are 105 agents in the AD drug development pipeline in phase 1-3 trials.  Seventy percent of these agents are disease modifying treatments whereas the remainder are in the form of cognitive enhancers and symptomatic agents5.  Further research into the genetic, molecular and mechanistic nature of AD is an essential step towards furthering the development of disease modifying treatments that will slow or halt the progression of AD6.  Bethyl manufactures many antibodies to proteins involved in AD that may aid in advancing breakthroughs and developing effective treatments.

 

Detection of mouse IP3R1 (red) and Nucleolin (green) in FFPE cerebellum by IHC-IF

Detection of mouse IP3R1 (red) and Nucleolin (green) in FFPE cerebellum by IHC-IF. Antibodies: Rabbit anti-IP3R1 (A302-158A) and rabbit anti-Nucleolin (A300-711A). Secondaries: DyLight® 594-conjugated goat anti-rabbit IgG (A120-201D4) and DyLight® 488-conjugated goat anti-rabbit IgG (A120-201D2).

Detection of mouse IP3R1 (red) and Nucleolin (green) in FFPE cerebellum by IHC-IF

Detection of mouse IP3R1 (red) and Nucleolin (green) in FFPE cerebellum by IHC-IF.  Antibodies: Rabbit anti-IP3R1 (A302-158A) and rabbit anti-Nucleolin (A300-711A). Secondaries: DyLight® 594-conjugated goat anti-rabbit IgG (A120-201D4) and DyLight® 488-conjugated goat anti-rabbit IgG (A120-201D2).  Counterstain: DAPI (blue).

Detection of human and mouse GAPDH by WB of HeLa, 293T, Jurkat, mouse TCMK-1, and mouse NIH3T3

Detection of human and mouse GAPDH by WB of HeLa, 293T, Jurkat, mouse TCMK-1, and mouse NIH3T3.  Antibody: Rabbit anti-GAPDH antibody (A300-639A).  Secondary: HRP-conjugated goat anti-rabbit IgG (A120-101P).

 

Below is the entire list of targets involved in Alzheimer's research. Can’t find what you are looking for? Bethyl offers a custom antibody service.

 

References

1. NIA (National Institute on Aging), 2017. Alzheimer’s Disease Fact Sheet [Internet]. [Cited 15 Dec 2017] Available from https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet

2. AA (Alzheimer’s Association), 2017. What is Dementia? [Internet]. [Cited 15 Dec 2017] Available from https://www.alz.org/what-is-dementia.asp

3. Jan AT, Azam M, Rahman S, Almigeiti AMS, Choi DH, Lee EJ, Haq, QMR, Choi I. 2017. Perspective insights into disease progression, diagnostics, and therapeutic approaches in alzheimer’s disease: a judicious update. Front Aging Neurosci. Nov 1;9:356.

4. Sen D, Majumder, Arora V, Yadu N, Chakrabarti R. 2017. Taming Alzheimer’s disease: new perspectives, newer horizons. Iran J Neurol. Jul 6;16(3):146-155.

5. Cummings J, Lee G, Mortsdorf T, Ritter A, Zhong K. 2017. Alzheimer’s disease drug development pipeline:2017. Alzheimers Dement. Sep;3(3):367-384.

6. Sun Q, Xie N, Tang B, Li R, Shen Y. 2017. Alzheimer’s disease: from genetic variants to the distinct pathological mechanisms. Front Mol Neurosci. Oct 6;10:319.