Are Infections the Seeds for Alzheimer's?

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Dec 01, 2023

scope image — Photo by Michael Schiffer on Unsplash

What causes Alzheimer’s disease (AD)? Nobody really knows. The prevailing theory is the amyloid cascade hypothesis which is based on the belief that amyloid plaques develop in the brain but have no function. However, as these plaques develop and expand they negatively impact cognition and memory. Since in this hypothesis it is believed that amyloid only have negative impacts (no biological function) research has been focused on its removal. In fact, it has been the focus of over 400 research studies costing tens of billions of dollars with very limited and disappointing results. The two recently FDA approved AD drugs, LEQEMBI and Aduhelm, focus on amyloid removal but haven’t improved anybody’s cognition or memory.

Lifestyle and genetic factors also play a role and the likely reality is multiple items may be involved in developing AD.

One theory, which has been downplayed as fringe for decades, is gaining momentum. The infection hypothesis states that a pathogen (e.g. bacteria, virus, fungi, parasite) makes it through the blood brain barrier into the brain and amyloid plaque is formed to protect the brain from this assault. It is the first line of defense that stops the pathogen from causing brain inflammation and destroying brain cells. In this theory amyloid isn’t the cause of the disease but the result of an insult (attack) on the brain. Here’s a quick 3 minute video explaining it by Rob Moir from Harvard University.

The most relevant parts of the video are:

Amyloid is a concrete like substance
Amyloid tombs and traps infections
Amyloid is a natural antibiotic
Amyloid rises when a virus or bacteria gets into the brain (likely to address the assault)
As amyloid increases they become toxic to brain cells which leads to neurodegeneration (eg. brain cells die)
It may be possible in the future to treat the infection agent upstream before they get into the brain and cause amyloid to form

It doesn’t surprise me that there is an infection / cognition connection. Memory care facilities routinely test and treat urinary tract infections when residents become more agitated and less lucid than normal.

In another video by Dr. Moir, he indicates that amyloid is 100 fold more effective as an antibiotic than penicillin1 and is part of the brain’s innate immune system.

Data that Associates Infection with AD is Broad

Per my April 17, 2023 post Is Preventing Alzheimers as Easy as Brushing Your Teeth?, oral bacteria is highly associated with AD. 90% of brain tissue from AD sufferers contain the bacteria that causes gingivitis2.

Other infections associated with AD are: Herpes simplex virus-1 (HSV-1)3, Espstein-Barr4, meningitis5, Chlamydia pneumoniae6 and others.

A Taiwanese study7 of 30,000 people with herpes simplex determined that individuals with chronic infections are 2 1/2 times more likely to develop AD but the good news is that several 100 sufferers who took anti-herpes medication were able to baseline such that their AD risk was the same as a person who didn’t have chronic herpes. Another Taiwanese study concluded that people with the Chlamydia pneumoniae infection have a 60% increase risk of AD but the risk is substantially reduced with anti-viral drugs8

It appears that while various infections can increase the likelihood of contracting AD; proper treatment can substantially reverse or minimize the infections’ impact.

The variety of pathogens that may cause AD is similar to pneumonia which can be triggered by bacteria, viruses or even food particles. This is problematic from a treatment perspective since there are different medications that address bacteria, viruses, fungi and parasites. Determination of the proper treatment requires knowing which pathogen(s) is the trigger.

You may want to review Multi-pathogen infections and Alzheimer’s disease for a very detailed description on how complex identifying and treating AD can be when caused by multiple pathogens.

Should AD be Treated as an Infectious Disease?

The answer is likely yes but not right now. It is too premature. Neurologists and other doctors that treat AD sufferers have limited backgrounds in infectious diseases, are siloed across medical specialties and treatment protocols don’t exist. But there is hope in the Alzheimer’s Pathobiome Initiative published by the Intracel Research Group. Per their website:

The Alzheimer’s Pathobiome Initiative is a global interdisciplinary collaboration to clarify the role of microbes in Alzheimer’s Disease, other dementias, and beyond.

This non-profit is focused specifically on microbes (infections) and their relationship with AD. In June of ‘23 they published a 23 page roadmap entitled Establishment of a consensus protocol to explore the brain pathobiome in patients with mild cognitive impairment and Alzheimer's disease. The abstract from the roadmap states:

Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer's disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer's Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post mortem brains versus cerebrospinal fluid, blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, polymerase chain reaction and sequencing techniques, and bioinformatic tools will be evaluated, in addition to direct microbial culture and metabolomic techniques. The goal is to provide a roadmap for detecting infectious agents in patients with mild cognitive impairment or AD. Positive findings would then prompt tailoring of antimicrobial treatments that might attenuate or remit mounting clinical deficits in a subset of patients.

There are a lot of words here but essentially they are doing the leg work to identify which pathogens may trigger an AD immune response (amyloid), how these pathogens function and their corresponding treatment. They will solicit input from across medical disciples and incorporate infection experts when appropriate. It may be several years before they publish their conclusions but at least they are started.

Currently, 85% of all AD research dollars are spent working on the amyloid cascade hypothesis (e.g. attacking the plaques in the brain). I’m glad to see a different, more upstream approach, getting traction.

The founder of the Intracell Research Group is Nikki Schultek who was prompted to start the non-profit because of her personal experience with an infectious disease. From the Intracell website:

Shortly after accepting her most treasured role, “mom”, Nikki fell ill with multiple autoimmune disorders to include frightening neurodegenerative symptoms. Noticing that physician specialists thought only within their “silo”, she started scouring the medical literature, discovering a strong correlation between her diagnoses and various chronic infections. Antibiotic treatment led to a complete remission (see full story in blog), and she is spending her life helping patients by asking fundamental questions about the role of infection in devastating diseases, with particular interest in neurodegeneration, Alzheimer’s Disease and Asthma. She is connecting researchers, clinicians, and stakeholders across the globe, building research collaborations, serving as a scientific and business advisor to companies innovating in this space, and publishing alongside global experts.

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