Alzheimer’s Disease Types and Causes

Alzheimer’s Disease is the most common type of dementia, which is an umbrella term used to describe a set of neurodegenerative diseases that affect memory and behavior, and eventually, make it difficult to accomplish basic functions like swallowing (2013 Alzheimer’s disease facts and figures). It’s a fatal disease with prolonged preclinical and prodromal phases that averages 20 years as well as an average clinical duration of 8–10 years (Masters et al., 2015). In order to meet the DSM-IV criteria for dementia, patients’ symptoms must have a decline in both memory and at least one of the following cognitive abilities: speak coherently or understand spoken or written language, recognize objects, be able to perform motor activities if the patient had motor abilities before diagnosis, think abstractly, make sound judgments, and plan and carry out complex tasks (2013 Alzheimer’s disease facts and figures). For the 65 years of age and above population, the disease has an estimated prevalence of 10–30%, and an incidence of 1–3%(Masters et al., 2015).

The signature of this disease is the formation of amyloid-β (Aβ) oligomers. These oligomers that gradually appear with old age aggregate into insoluble amyloid plaques that can be found throughout the neural tissue. The soluble form of these oligomers is linked to cell toxicity and general neurodegenerative symptoms found in Alzheimer’s patients.Aβ oligomers are formed by the cleavage of the amyloid precursor protein (APP) via β-secretase and γ-secretase. There are two known types and an emerging third type of Alzheimer’s Disease: sporadic, familial, and the newly found third type that is linked to type 2 diabetes.

Figure 1. Amyloid Beta Peptide

There have been a range of tools used to diagnosis Alzheimer’s Disease. Aβ PET imaging has been used to detect amyloid-β plaques in the brain. A build up of this plaque is common in old age, and is not the most reliable form to fully diagnose a patient. However, studies have confirmed that Aβ deposits begin decades before dementia. It also precedes cognitive decline and brain atrophy (Del Sole, A., 2016). Another way to diagnose Alzheimer’s is plasma protein filing for biomarkers. In a study released in 2017, researchers retrieved plasma samples from mild Alzheimer’s disease patients and tested for prevalence of apolipoproteins and glycoproteins. They were able to find that certain forms of apolipoproteins and glycoproteins were down regulated, which were expected with these patients (Kitamura, Y. et al., 2017). A common method used for diagnosis is cerebral spinal fluid (CSF) profiling. CSF collection via lumbar puncture is done to identify and track several known biomarkers of Alzheimer’s disease which include Aβ42, total-tau (T-tau), and phosphorylated-tau (P-tau) (McKhann et al., 2011). However, it is still challenging to properly diagnosis, especially in the prodromal stage when patients only have slight cognitive irregularities. It is especially difficult when co-morbidities like cerebrovascular disease is already present in a patient as it gets in the way of properly diagnosing.

The sporadic form of Alzheimer’s disease is the most common form filling 95% of total cases reported. It’s late onset usually effecting the 80-90 years of age population (Masters et al., 2015). The hallmark of sporadic Alzheimer’s disease is the failure of clearing the amyloid-β peptide from the crevices of the brain. Recent findings have led researchers to believe that epigenetic mechanisms play a key role in this form of the neurodegenerative disease (Piaceri, I., 2013). Other common diseases at this age range such as cerebrovascular disease complicates diagnosis and management of Alzheimer’s disease(Masters et al., 2015).

The familial form of Alzheimer’s Disease hits a small portion of reported cases (>1%). It is also known as autosomal dominant inherited Alzheimer’s disease (DIAD). This form has an early age of onset between 40 and 50 years of age. This group is characterized by the pathogenetic mutations in the genes encoding APP, PSEN1, and PSEN2, which cause overproduction or formation of Aβ oligomers. In most clinical cases, the sporadic and familial forms of Alzheimer’s disease are quite similar in the rate of disease progression and various biomarker profiles.

The new third form of Alzheimer’s disease involves a clear link between the neurodegenerative disease and type 2 diabetes. In a study conducted in 2016 in which Zhang et al. reviewed various longitudinal studies concerning elderly patients and Alzheimer’s, they found an increasing rate of cognitive decline in elderly people with type 2 diabetes (Zhang et al., 2016). More on the biochemistry of this form of Alzheimer’s disease can be found on the page “Disease Mechanism: A Biochemical View of How Alzheimer’s Disease and Type 2 Diabetes are Linked”.

2 Replies to “Alzheimer’s Disease Types and Causes

  1. Hi Aisha, thank you for the enlightenment in this obscure world of Alzheimer.
    Nice Work!
    Would you please clarify for me in layman’s term the difference between the sporadic form and the new third form of Alzheimer’s Disease since they both seem to be linked to type 2 diabetes?

    1. Hi Dad!
      Thank you so much for making it on to the expert/peer pages.
      The third form of Alzheimer’s disease I described is the sporadic form, but sporadic cases that have been linked to type 2 diabetes. Not all cases of the sporadic form of Alzheimer’s disease is linked to type 2 diabetes, but there have been an increasing amount of cases that show the two diseases “working” together.
      Thank you for reading my posts!

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