The major subtypes of Alzheimer’s disease.
Identified just over a century ago, Alzheimer’s disease is a complex, multifaceted condition that affects nearly 44 million people worldwide. Dr. Dale Bredesen identified the defining characteristics of Alzheimer’s disease and discovered there are 5 distinct subtypes, each requiring different treatment: Type 1 inflammatory, Type 1.5 glycotoxic, Type 2 atrophic, Type 3 toxic, Type 4 vascular, and Type 5 traumatic.
The inflammatory subtype of Alzheimer’s disease.
A type characterized by systemic inflammation, reflected in such laboratory results as a high hs-CRP (high-sensitivity C-reactive protein), low albumin:globulin ratio, and high cytokine levels such as interleukin-1 and interleukin-6.
The atrophic subtype of Alzheimer's disease — a reduction in support for synaptogenesis.
A type characterized by an atrophic profile, with reduced support from molecules such as estradiol, progesterone, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), testosterone, insulin, and vitamin D, often accompanied by increased homocysteine and insulin resistance, the last feature of which Dr. Bredesen refers to as type 1.5 or glycotoxicity (sometimes called type 3 diabetes).
The cortical subtype of Alzheimer's disease — an environmental toxin-related type associated with chronic Inflammatory response syndrome (CIRS) that presents with more general cerebral atrophy and frontal-temporal-parietal abnormalities, resulting in an emphasis on executive deficits, rather than the more amnestic quality of hippocampal impairment.
Although the subtypes vary in their causes and manifestation and often overlap to some degree, Dr. Bredesen explains that the underlying pathological features – the accumulation of amyloid beta plaques and tau tangles – are unifying aspects of the disease. He adds that how these features play out in the somewhat fragile environment of the brain depends on a wide array of contextual parameters, such as genetics and lifestyle factors, including diet, sleep, exercise, and environmental exposures.
Amyloid-beta as an antimicrobial response:
Amyloid-beta is a protein fragment that has long been implicated in the pathogenesis of Alzheimer’s disease. It is a known neurotoxin that destroys nerve synapses and then clumps into plaques that lead to nerve cell death. But in recent decades research has revealed interesting characteristics that suggest amyloid-beta can play a protective role against fungal, bacterial, and viral infections.
One example is seen in the herpes virus, which upregulates the production of amyloid-beta protein in vitro. In turn, the protein binds to and agglutinates the viral particles. Perhaps more importantly, increased production of amyloid-beta improves survival in animals subjected to a viral assault, a phenomenon that strongly supports an antimicrobial protection hypothesis of Alzheimer’s disease. There may be good reason for this antimicrobial property too: 90% of glioblastomas, a type of brain cancer, have been shown to express a herpes type of virus known as cytomegalovirus. Most people harbor latent herpes virus infections, and some evidence suggests that reactivation of the latent virus in the brain, particularly in APOE4 carriers, might increase the risk of developing Alzheimer’s disease.
The interaction of metals with amyloid-beta:
One of the roles amyloid-beta may also play as “protector” is that of binder of transition metals like zinc, copper, or iron. Animal experiments demonstrate that chelating agents can even reduce deposition of amyloid-beta. These interactions with metals become important in the discussion of Dr. Bredesen’s protocol where a combination of early-onset, non-amnestic cognitive changes, and biomarkers like altered copper-to-zinc ratio, especially low serum zinc, might be suggestive of the “cortical” or “toxic” subtype of Alzheimer’s disease..
The role of the APOE4 polymorphism in Alzheimer’s disease:
More than 75 million people in the US carry at least one allele for APOE4, a version of apolipoprotein E that is the major genetic risk factor for Alzheimer’s disease, which some studies show may increase the odds of developing Alzheimer’s disease by as much as 2- to 3-fold in the case of heterozygotes and as much as 15-fold in homozygotes. The old mantra – that little could be done to prevent APOE-related Alzheimer’s disease – is now being challenged, however. Dr. Bredesen’s research indicates that, armed with knowledge, we can make dietary and lifestyle changes to prevent or at least delay the cognitive losses that once seemed to be one’s destiny.
The biomarkers of Alzheimer’s disease and the Bredesen Cognoscopy
A key element in the acquisition of knowledge about our risks factors and what can be done to manage our risks is what Dr. Bredesen calls a “cognoscopy” – a term he coined that describes a battery of assessments, including biochemical tests, which measure some of the key biomarkers for Alzheimer’s disease.
Dr. Bredesen proposes a pretty radical idea: Alzheimer’s disease as we know it could be largely ended with the current generation. The key to doing this? By treating the prevention of Alzheimer’s in much the same way we treat colon cancer — with screening to detect the first signs of trouble. However, a recurring theme Dr. Bredesen brings up is that what most labs and clinicians call normal may actually be different than what is optimal. His view is that not only should we potentially get tested and keep an eye on certain biomarkers in particular, but more importantly, for some of these tests, our goal should be to keep our ranges even healthier than what the laboratory references may indicate as “normal.”
Whether a person is at risk of developing the disease versus actively manifesting symptoms is often reflective of the number of their suboptimal biomarkers: as few as three to five suboptimal lab values may be observed in an at-risk pre-symptomatic person versus up to 25 in a symptomatic person. (See chapter 7, The "Cognoscopy" — Where Do You Stand? in Dr. Bredesen’s book The End of Alzheimer’s)
Dr. Anne Chappel has been trained by Dr. Bredesen personally, and seen his successes first hand. She is now offering this cutting edge approach to cognitive decline reversal to our patients. If you would like to discuss your personal experience and have a tailor-made solution for your cognitive health, book in with Dr Anne Chappel at Evergreen Doctors today.
Read the Studies:
Reversal of Cognitive Decline in Alzheimer’s Disease
Alzheimer’s disease is one of the most significant healthcare problems nationally and globally. Recently, the first description of the reversal of cognitive decline in patients with early Alzheimer’s disease or its precursors, MCI (mild cognitive impairment) and SCI (subjective cognitive impairment), was published. The therapeutic approach used was programmatic and personalized rather than monotherapeutic and invariant, and was dubbed metabolic enhancement for neurodegeneration (MEND). Patients who had to discontinue work were able to return to work, and those struggling at work were able to improve their performance. The patients, their spouses, and their co‐workers all reported clear improvements. READ THE STUDY
Reversal of Cognitive Decline: 100 Patients
The first examples of reversal of cognitive decline in Alzheimer’s disease and the pre-Alzheimer’s disease conditions MCI (Mild Cognitive Impairment) and SCI (Subjective Cognitive Impairment) have recently been published. These two publications described a total of 19 patients showing sustained subjective and objective improvement in cognition, using a comprehensive, precision medicine approach that involves determining the potential contributors to the cognitive decline (e.g., activation of the innate immune system by pathogens or intestinal permeability, reduction in trophic or hormonal support, specific toxin exposure, or other contributors), using a computer-based algorithm to determine subtype and then addressing each contributor using a personalized, targeted, multi-factorial approach dubbed ReCODE for reversal of cognitive decline.
An obvious criticism of the initial studies is the small number of patients reported. Therefore, we report here 100 patients, treated by several different physicians, with documented improvement in cognition, in some cases with documentation of improvement in electrophysiology or imaging, as well. This additional report provides further support for a randomized, controlled clinical trial of the protocol and the overall approach. READ THE STUDY
Transcriptional Effects of ApoE4: Relevance to Alzheimer's Disease
The major genetic risk factor for sporadic Alzheimer's disease (AD) is the lipid binding and transporting carrier protein apolipoprotein E, epsilon 4 allele (ApoE4). One of the unsolved mysteries of AD is how the presence of ApoE4 elicits this age-associated, currently incurable neurodegenerative disease. Recently, we showed that ApoE4 acts as a transcription factor and binds to the promoters of genes involved in a range of processes linked to aging and AD disease pathogenesis. READ THE STUDY
Downregulation of protein phosphatase 2A by apolipoprotein E: Implications for Alzheimer's disease.
The apolipoprotein E ε4 allele is the single most important genetic risk factor associated with Alzheimer's disease (AD). Tau phosphorylation and hyperphosphorylation is an underlying feature of AD and is regulated by specific kinases and phosphatases. Among phosphatases, protein phosphatase 2A (PP2A) is the principal tau dephosphorylating enzyme in the brain. Several abnormalities of PP2A have been reported in AD, including among others decreased protein levels of PP2A, decreased mRNA and protein levels of the catalytic subunit PP2AC and variable regulatory B subunits and reduced methylation of the catalytic subunit, all of which results in disruption of the PP2A phosphatase activity. READ THE STUDY