Alzheimer's - Beyond Genetics

Have your family or friends been afflicted by Alzheimer’s (AD), and do you worry about whether you, or another loved one, might be at risk? If so, we’re here to help.

Around 850,000 people in the UK live with cognitive decline (or ‘dementia’) and over 1 million may be affected by 2025 if we continue at the rate we’re going.[i]

AD is the overriding cause. The most prevalent subtypes are late-onset AD (LOAD), the most common form, which starts during older age (c. 65 years +), and early-onset AD which affects younger individuals (c. 30-65 years).

Key signs of cognitive decline[ii]:

• Minor memory problems which become more severe with time
• Confusion and getting lost in familiar places
• Difficulty with decision making, planning, speech, and language
• Personality changes e.g. becoming aggressive
• Hallucinations and delusions
• Low mood

You may have also heard about the role of genetics, especially the ‘APOE’ gene, causing you more worry about whether you carry the problematic variants (or ‘SNP’s’), which everyone is talking about.[iii] We hope that this blog reassures you that genetics, or APOE, are only one piece of a large, complex jigsaw behind why AD develops, and empowers you with the knowledge of how you can support yourself.

The APOE gene

AD develops when two types of protein, amyloid beta (Aβ) and tau, build up within the brain,[iv] causing abnormal structures to form called plaques and neurofibrillary tangles. These injure neural connections, triggering neurodegeneration and dementia.[v]

Apolipoprotein E (ApoE), coded by the APOE gene,[vi] supports the growth and repair of neurons by transporting the essential substrate – cholesterol - around the brain. It also helps regulate the metabolism of Aβ in the brain and lipids in the bloodstream.[vii]^,[viii] SNPs of the APOE gene are the main genetic risk factor for LOAD, especially the APOE ε4 allele.[ix] Those of us who carry this SNP seems to be more prone to AD related to a tendency towards poorer regulation of Aβ[x]and blood lipids, repair of neurons, and recovery from traumatic brain injury.[xi] These changes contribute to neurotoxicity, reduction in size of brain regions involved in memory (e.g. hippocampus),^[xii] and deterioration of cardiovascular health,[xiii] all of which are recognised as driving forces of this disease. However, there are a wide range of other factors, which are well within our control, which can influence how significant this SNP actually becomes for our cognitive and all-round health.

Beyond Genetics

• Low levels of acetylcholine, a messenger molecule (or ‘neurotransmitter’) involved in memory, are associated with dementia.[xiv] This may result from not eating enough choline rich foods, such as egg yolks and offal, alongside existing damage to nerve cells which can worsened by neurotoxic levels of the stimulatory neurotransmitter called glutamate.[xv] This can arise if we are under sustained stress, don’t sleep very well, consume monosodium glutamate (MSG) from take-aways, and convert glutamate to the more calming neurotransmitter, GABA, too slowly. Poor glutamate to GABA conversion can be caused by low levels of vitamin B6,[xvi] and genetic polymorphism of the gene responsible for this called ‘GAD’.[xvii] Chronic stress also injures brain regions involved in memory via the release of cortisol[xviii] and drives inflammation, another risk factor for AD.[xix]^,[xx]Meanwhile, poor sleep allows Aβ to accumulate in the brain,[xxi] even after just one night of sleep deprivation![xxii]
• The brain can find it hard to self-repair (neuroplasticity) due to factors beyond just APOE. The main ones to know about are not consuming enough omega-3[xxiii] from oily fish and flaxseeds, and having a sedentary lifestyle. BDNF (brain-derived neurotrophic factor) is a messenger molecule which promotes the growth, development, and repair of neurons. Exercise is one of the best ways to boost the level of BDNF.[xxiv] So, a lack of exercise may contribute towards low circulating levels of BDNF, as observed in individuals with AD.[xxv]^,[xxvi]
• Neurotransmitters need to communicate with healthy cell membranes to properly convey the messages which they are carrying. If we consume too much omega-6 from grains and conventionally reared meat, too little foods rich in omega-3, and have a diet low in antioxidant- and phospholipid- rich foods like berries and offal, our cell membranes can become damaged and inflexible and less responsive to this signalling. Brain cells, and the energy powerhouses within our cells called mitochondria, are particularly prone to oxidative damage, so any driver of this, especially smoking, [xxvii]^,[xxviii] air pollution,[xxix] and high blood sugar,[xxx] may contributes towards neurodegeneration.[xxxi],[xxxii]
• Individuals with Type 2 Diabetes Mellitus generally have an increased risk of AD, whether or not they carry the APOEε4 allele,[xxxiii] leading researchers to describe it as ‘brain diabetes’ or even, ‘Type 3 Diabetes Mellitus’.[xxxiv] Blood sugar imbalance caused by a diet rich in carbohydrates (e.g. pasta, bread), regular snacking, and a sedentary lifestyle are therefore key risk factors. A lack of exercise also impairs neuroplasticity,[xxxv] and regular snacking keeps us in a constant fed state, which inhibits the process of autophagy, our brain’s way of cleaning itself and removing excess Aβ.[xxxvi]
• Homocysteine is a substance naturally produced in the body however, at higher amounts it can increase oxidative stress and accumulation of Aβ.[xxxvii] The biological process of methylation is needed to regulate it and also, produce enough of the neurotransmitter dopamine which is involved in memory too.[xxxviii] So, poor methylation driven by SNPs of key genes such as ‘MTHFR’,[xxxix] not consuming enough folate[xl] and B12[xli] from green leafy vegetables and grass-fed, organic meat, and being exposed to ‘drains’ on methylation such as alcohol,[xlii] may contribute to the complex picture of neurodegeneration.
• The role of neuroinflammation is generally becoming accepted too,[xliii] forcing us to recognise the potential role of any mediator of inflammation which we’re exposed to, ranging from processed food[xliv] to poor gut health[xlv]^,[xlvi] and latent infections.[xlvii]
• Being exposed to heavy metals, like aluminium from tap water^[xlviii] and mercury from dental amalgams,^[xlix] can also increase our risk,^[l] especially if we have a reduced ability to detoxify them due to inadequate levels of glutathione, our body’s own antioxidant, related to dietary and genetic factors.[li]

So AD is caused by a conspiracy of different factors, combining together, to drive neurodegeneration and dementia. There’s not one single cause! While on one level this may still seem scary, it is actually empowering because it means that there is much that we can do to help ourselves.

How to support cognition

• Vitamin B5 and choline to support acetylcholine production.^[lii],[liii] Choline is also needed to make phosphatidyl choline, a component of cell membranes.
• Vitamin B6 to encourage conversion of glutamate to GABA, and magnesium,^[liv] taurine,^[lv]chamomile,[lvi]^,[lvii] L-Theanine,[lviii],[lix] and lemon balm[lx]^,[lxi] to further increase the activity of GABA, to improve stress management and sleep.[lxii] Sleep may also support the clearance of Aβ from the brain,[lxiii] so optimising sleep is an essential goal. Consider complementary lifestyle techniques such as sleeping in a dark room and meditation.[lxiv]
• Omega-3 to support neuroplasticity, alongside daily exercise[lxv] to boost acetylcholine[lxvi] and BDNF levels, as well as cell membrane structure,[lxvii] mood,^[lxviii] and inflammation.^[lxix] Further support cell membranes and cognition with phosphatidyl serine,[lxx] good fats (coconut oil, avocado, fish), and dietary antioxidants (e.g. flavonoids,^[lxxi]beta carotene,^[lxxii]vitamin C and E^[lxxiii]), and nutrients to support the body’s antioxidant enzymes (e.g. zinc^[lxxiv]). Curcumin from turmeric may provide comprehensive neuroprotection by inhibiting both Aβ and inflammation.^[lxxv]
• Minimise contact sports, which come with a risk of head trauma. Explore brain training techniques (e.g. learn a language or a new instrument).[lxxvi]
• Magnesium,[lxxvii]D-ribose,[lxxviii]N-acetyl carnitine,^{[lxxix],[lxxx]} and vitamin B2 and B3^[lxxxi] to support mitochondrial function and in turn, neuronal function.
• Botanicals, such as Ginkgo,^[lxxxii] saffron,[lxxxiii]blackcurrant,^[lxxxiv] and sage,[lxxxv] which may support cognition.
• Quit smoking, enjoy a homemade wholefood diet, explore safe removal of mercury amalgams, and drink filtered or glass bottled water.
• Chromium^[lxxxvi] and alpha lipoic acid[lxxxvii]^,[lxxxviii] to support regulation of blood sugar, alongside daily exercise, avoidance of snacking, and a Paleo style way of eating.
• Explore time restricted feeding, or fasting, guided by a health professional, to support blood sugar balance and the brain’s ability to clean itself via autophagy.[lxxxix]
• Folate, B12, and B6 to support methylation and so, high homocysteine,^[xc],[xci] as well as stress levels,[xcii] mood,[xciii] memory, detoxification,[xciv] and cell membrane structure,[xcv] alongside reduced exposure to ‘drains’ (e.g. alcohol).
• Support detoxification of heavy metals via methylation and glutathione conjugation with added reduced glutathione or N-acetyl cysteine.[xcvi]^,[xcvii]
• Probiotics to support the beneficial bacteria in the gut and the integrity of the gut wall, especially if you experience digestive issues such as food sensitivities and constipation.[xcviii]

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