Alzheimer's disease consists of 3 distinct subtypes

  • A very small study points to three subtypes of Alzheimer's disease, each of which seems to be associated with:
    • different physiological abnormalities
    • different causes and risk factors
    • different symptoms / progression
    • different age-onsets.
  • This suggests that effective treatments need to be tailored to the subtype.

A two-year study which involved metabolic testing of 50 people, suggests that Alzheimer's disease consists of three distinct subtypes, each one of which may need to be treated differently. The finding may help explain why it has been so hard to find effective treatments for the disease.

The subtypes are:

  • Inflammatory, in which markers such as C-reactive protein and serum albumin to globulin ratios are increased.
  • Non-inflammatory, in which these markers are not increased but other metabolic abnormalities (such as insulin resistance, hypovitaminosis D, and hyper-homocysteinemia) are present. This tends to affect slightly older individuals than the first subtype: 80s rather than 70s.
  • Cortical, which affects relatively young individuals (typically 50s- early 70s) and appears more widely distributed across the brain than the other subtypes, showing widespread cortical atrophy rather than marked hippocampal atrophy. It typically presents with language and number difficulties first, rather than memory loss. Typically, there is an impaired ability to hold onto a train of thought. It is often misdiagnosed, typically affects people without a family history of Alzheimer's, who do not have an Alzheimer's-related gene, and is associated with a significant zinc deficiency (Zinc is implicated in multiple Alzheimer's-related metabolic processes, such as insulin resistance, chronic inflammation, ADAM10 proteolytic activity, and hormonal signaling. Zinc deficiency is relatively common, and associated with increasing age.).

The cortical subtype appears to be fundamentally a different condition than the other two.

I note a study I reported on last year, that found different molecular structures of amyloid-beta fibrils in the brains of Alzheimer's patients with different clinical histories and degrees of brain damage. That was a very small study, indicative only. However, I do wonder if there's any connection between these two findings. At the least, I think this approach a promising one.

The idea that there are different types of Alzheimer's disease is of course consistent with the research showing a variety of genetic risk factors, and an earlier study indicating at least two pathways to Alzheimer's.

It's also worth noting that the present study built on an earlier study, which showed that a program of lifestyle, exercise and diet changes designed to improve the body's metabolism reversed cognitive decline within 3-6 months in nine out of 10 patients with early Alzheimer's disease or its precursors. Note that this was a very small pilot program, and needs a proper clinical trial. Nevertheless, it is certainly very interesting.

http://www.eurekalert.org/pub_releases/2015-09/uoc--adc091615.php

Reference: 

Bredesen, D.E. 2015. Metabolic profiling distinguishes three subtypes of Alzheimer's disease. AGING, 7 (8), 595-600. Full text at http://www.impactaging.com/papers/v7/n8/full/100801.html

Bredesen, D.E. 2014. Reversal of cognitive decline: A novel therapeutic program. AGING, Vol 6, No 9 , pp 707-717. Full text at http://www.impactaging.com/papers/v6/n9/full/100690.html

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