Review: Alzheimer’s Disease

For the first official post of this blog I thought it would be a good idea to talk about a topic that most people have had some exposure to, one in which Alzheimer’s disease. Firstly, let us answer the question as to what Alzheimer’s disease is.  According to the Alzheimer’s disease Association: “Alzheimer’s is a type of dementia that causes problems with memory, thinking and behavior.“ It is also by far the most common type of dementia. Needless to say, this topic is of the utmost importance, exceptionally so because of humanity’s discoveries in modern medicine allowing us to live for longer periods of time than ever before.

To move forward we should address what makes Alzheimer’s disease different from other said types of dementia, i.e. Lewy Body dementia, Mild Cognitive Impairment, Parkinson’s disease dementia, et cetera. In terms of molecular biology Alzheimer’s disease presents itself with the presence of Beta Amyloid Plaques as well as Neurofibrillary tangles.

Beta Amyloid Plaques

Beta peptides are created through the breakdown of larger proteins via a proteolytic process (breakdown of proteins into single peptides). These peptides are broken down from the original protein the Amyloid Precursor Protein (APP) which is found throughout the central nervous system (brain and spinal cord) (Masliah, 2009). It is the aggregation of these amyloid beta peptides that create the hallmark amyloid beta plaques which are extremely toxic to neurons (brain cells). Via Caspase-3 activation, apoptosis occurs in the hippocampus (the area of the brain that is thought to be responsible for the formulation of new memories) (D’Amelio, 2011).This may explain why many individuals with AD dementia have a difficulty incorporating new memories.

Neurofibrillary Tangles

In the axon of a neuron there are long skeletal structures of the cell called microtubules. These microtubules are normally responsible for giving the cell structure and support as well as serving as a sort of rail road for the transportation of nutrients throughout the cell. These microtubules are amalgamated together via a protein by the name of tau. In Alzheimer’s disease tau proteins begin to have detrimental effects by disassembling from the microtubules. Once disassembled the tau begins to cluster together and disrupts the normal functioning of the cell. This process will eventually kill the neuron (Hoover et. al 2010).

Here is a youtube video that is quite helpful in better understanding biology behind these processes.

Here is an interesting quote that explains how there may be a connection between Neurofibrillary tangles and the Beta Amyloid Plaques

“Although amyloid plaques and NFTs have been largely regarded as independent neuropathologic entities, recent work suggests they may be functionally linked: mutation of APP that results in amyloid deposition or direct intracranial injection of A peptide increases NFT formation in transgenic mice expressing an FTDP-17-causing tau mutant” (Hoover et. al. 2010).

The genetic component of Alzheimer’s disease seems to be a promising route in the hunt for the cure, however one should realize that there is not a 100% incidence rate with the possession of the ApoE-4 polymorphism. First, we should understand what ApoE does before talking about the problems that can occur with the possession of the gene. ApoE maintains and regulates the redistribution as well as the mobilization of cholesterol during growth and repair and maintenance of a neuron’s myelin and neuronal membranes. ApoE is activated during developmental phases or following injury. However, ApoE mRNA is also found in Beta Amyloid plaques.

“Furthermore, if apoE disrupts lipase activity24 in the brain and alters the transport of cholesterol and phospholipids in brain areas vulnerable to ageing, a direct consequence would be aberrant and/or defective reinnervation and poor synaptic plasticity. For example, reports on cerebral cortex integrity in AD have revealed a 45 % decrease in presynaptic terminal density in the neocortex25 and significant synaptic losses in the frontal and temporal cortices” (Poirier et. al. 1993).

An important task that many scientists are still working countless hours upon is the testing and discovery of diagnostic tests. The national institute on Ageing-Alzheimer’s Association has indicated that there are a number of biomarker tests that are promising but more research regarding these tests need to be done in order for validation to stand on solid ground. At the current time a battery of Neuropsychological tests and scans are in all likelihood the only tests that are conducted in order to order the diagnosis of AD (McKhann, 2011). Many physicians and neuropsychologists also refer to self-report as well as an informant’s report to help them better understand each individual’s case. The most definitive way to currently get a diagnosis is unfortunately during autopsy at which point a pathologist will look for the hallmark Beta Amyloid plaques and Neurofibrillary tangles.

Last but not least is a list of preventative steps and health tips in hopes of avoiding AD.

A. Solomon et al. Key Symposium: Prevention of Alzheimer’s disease and dementia

“Table 1 Proposed risk and protective factors for late-onset dementia and Alzheimer’s disease Risk factors


Genetic Familial aggregation APOE e4 Different genes (e.g. CR1, PICALM, CLU, TREM2, TOMM40) have been proposed (

Vascular and metabolic Cerebrovascular lesions Cardiovascular diseases Diabetes mellitus and pre-diabetes

Midlife positive association but late-life negative association Hypertension High BMI (overweight and obesity) High serum cholesterol

Lifestyle Smoking High alcohol intake


Saturated fats Low B vitamins/high homocysteine Homocysteine


Depression Traumatic brain injury Occupational exposure (heavy metals, ELF-EMFs) Infective agents (herpes simplex virus type I, Chlamydophila pneumoniae, spirochetes)

Protective factors

Genetic Different genes (e.g. APP, APOE e2) have been proposed ( Psychosocial factors High levels of education and SES High level of complexity of work Rich social network and social engagement Mentally stimulating activity Lifestyle Physical activity Moderate alcohol intake


Mediterranean diet PUFAs and fish-related fats Vitamins B6 and B12, folate Antioxidant vitamins (A, C and E) Vitamin D


Antihypertensive drugs Statins HRT


Combined effect Increased risk Genetic and environmental factors in midlife APOE e4 magnifies the effect of high alcohol intake, smoking, physical inactivity and high intake of saturate fat

Vascular and metabolic factors in midlife Co-occurrence of hypertension, obesity, hypercholesterolaemia and/or physical inactivity has an additive effect

Vascular and metabolic factors/diseases in late-life Higher risk in individuals with brain hypoperfusion profile: chronic heart failure, low pulse pressure, low diastolic pressure Higher risk in individuals with atherosclerosis profile: high systolic pressure, diabetes mellitus or prediabetes, stroke

Decreased risk Genetic and environmental factors in midlife High education level reduces the negative effect of APOE e4 Physical activity counteracts the risk due to APOE e4 Environmental factors in midlife High level of complexity of work modulates the increased dementia risk due to low level of education

Genetic and environmental factors in late-life Active leisure activities or absence of vascular risk factors reduces the risk due to APOE e4

APP, amyloid precursor protein; APOE, apolipoprotein E; BMI, body mass index; CLU, clusterin; CR1, complement component receptor 1; ELF-EMF, extremely low-frequency electromagnetic field; HRT, hormone-replacement therapy; NSAID, non-steroidal anti-inflammatory drug; PICALM, phosphatidylinositol binding clathrin assembly protein; PUFA, polyunsaturated fatty acid; SES socioeconomic status; TOMM40, translocase of outer mitochondrial membrane 40 homolog;TREM2, triggering receptor expressed on myeloid cells 2. A large number of risk and protective factors for dementia and Alzheimer’s disease have been investigated, and there are greater and lesser degrees of evidence to support these various factors” (Soloman et. al. 2014)


“Alzheimer’s Disease & Dementia | Alzheimer’s Association.” Alzheimer’s Disease & Dementia | Alzheimer’s Association. N.p., n.d. Web. 14 July 2014. <;.

Edge, L. (2011). Select: Molecular pathology of alzheimer’s disease. Cell, 144(3), 315-317. doi:10.1016/j.cell.2011.01.027

Gamblin, T. C., Chen, F., Zambrano, A., Abraha, A., Lagalwar, S., Guillozet, A. L., et al. (2003). Caspase cleavage of tau: Linking amyloid and neurofibrillary tangles in alzheimer’s disease. Proceedings of the National Academy of Sciences of the United States of America, 100(17), 10032-7. doi:10.1073/pnas.1630428100

Masliah,Eliezer (University of California San Diego). (2009). Molecular pathology of alzheimer’s disease. Plenary, 01(01), 2009-2009.

McKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack, C. R., Kawas, C. H., et al. (2011). The diagnosis of dementia due to alzheimer’s disease: Recommendations from the national institute on aging-alzheimer’s association workgroups on diagnostic guidelines for alzheimer’s disease. Alzheimer’s & Dementia : The Journal of the Alzheimer’s Association, 7(3), 263-9. doi:10.1016/j.jalz.2011.03.005

Poirier, J., Davignon, J., Bouthillier, D., Kogan, S., Bertrand, P., & Gauthier, S. (1993). Polymorphism and alzheimer ’ s disease. The Lancet, 342, 697-699.

Price, J. L., & Morris, J. C. (1999). Tangles and plaques in nondemented aging and ?preclinical? alzheimer’s disease. Annals of Neurology, 45(3), 358-368. doi:10.1002/1531-8249(199903)45:33.0.CO;2-X

Selkoe, D. J. (1991). The molecular of alzheimer ’ s pathology disease review. Neuron, 6, 487-498.

Solomon, a., Mangialasche, F., Richard, E., Andrieu, S., Bennett, D. a., Breteler, M., et al. (2014). Advances in the prevention of alzheimer’s disease and dementia. Journal of Internal Medicine, 275(3), 229-50. doi:10.1111/joim.12178


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