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Cholesterol and neurodegenerative disorders: a link that remains poorly understood?

2026-09-16

A recent study has examined the relationship between cholesterol and neurodegenerative disorders. This is a scientific avenue that is still emerging, but one that is becoming increasingly intriguing...

Could there be a link between cholesterol levels and cognitive decline?

Cholesterol and Alzheimer’s disease: what the study says

Whilst it is generally associated with cardiovascular disorders, cholesterol also plays a crucial role in the brain. It contributes to the structure of neuronal membranes and the transmission of signals between nerve cells (1).

A recent study suggests that a disruption in cholesterol metabolism in the brain could, in fact, contribute to several mechanisms involved in neurodegenerative disorders (including Alzheimer’s disease), notably brain inflammation, neuronal dysfunction and the progressive decline in cognitive function (2).

Brain lipid metabolism and neurodegenerative disorders: what are the links?

Neuroinflammation and the activation of brain immune cells

This review highlights the possible role of cholesterol in neuroinflammation. An imbalance in brain lipid metabolism could excessively activate certain immune cells in the brain, particularly microglia (which are responsible, amongst other things, for clearing cellular debris and abnormal proteins) (3). By releasing more inflammatory molecules, they may sustain the chronic low-grade inflammation implicated in neurodegenerative disorders.

Neuronal dysfunction

The brain relies on extremely rapid and coordinated communication between billions of neurons. However, cholesterol directly influences the quality of neuronal membranes and synapses. When poorly regulated, the transmission of nerve signals may therefore become less efficient (4).

Cognitive decline

Through the combined effects of neuroinflammation and impaired neuronal connections, poor lipid regulation may also affect synaptic plasticity, learning abilities and memory, leading to a gradual decline in cognitive function (5).

Oxidative stress and brain ageing

Oxidative stress is another avenue being investigated in neurodegenerative disorders. The brain consumes a significant amount of oxygen and has a high concentration of polyunsaturated lipids, making it particularly susceptible to oxidative processes. It therefore appears that disrupted lipid metabolism may render nerve cells more vulnerable to these repeated attacks and accelerate cellular ageing (6).

Can we influence cholesterol balance?

Cholesterol balance depends on many factors: diet, physical activity, sleep quality, stress management, overall metabolic balance, etc.

The aim is not to eliminate lipids, but to maintain a healthy balance between the different types of cholesterol. Certain nutrients and plant compounds are specifically studied for their interaction with lipid metabolism. They can form part of a holistic nutritional approach, complementing a healthy lifestyle.

Combined formulations designed to support cholesterol balance often combine various nutritional ingredients and plant extracts. Some, for example, combine natural statin-free (monacolin-free) red yeast rice with artichoke extract, which helps regulate blood lipid levels (7–8).

-This is the case with Cholesterol Complex Formula, which contains Ankascin® 568-P, a clinically studied, monacolin-free fermented red yeast rice with a remarkably broad spectrum of action (blood lipids, blood pressure, blood glucose levels, etc.).

Pantethine is a derivative of vitamin B5. This vitamin contributes to normal energy metabolism and mental performance. It also plays a role in the metabolism and indirect synthesis of several neurotransmitters, including acetylcholine, which is involved in memory and learning (9).

-Available in our Pantethine supplement.

Olive leaf, meanwhile, contains polyphenols such as oleuropein. It has antioxidant properties (which are thought to limit, in particular, the oxidation of ‘bad’ LDL cholesterol, known to weaken arterial walls) and helps maintain normal blood sugar levels (as an improved insulin response can indirectly improve lipid balance) (10–11).

-Olive Leaf Extract has an exceptionally high oleuropein content.

Supporting brain nutrition

Brain health depends on a complex set of nutritional and physiological factors. The brain has specific requirements for nutrients involved in neuronal function to ensure, amongst other things, energy production, cellular signalling and protection.

Certain nutritional approaches therefore aim to support the brain in the face of cognitive ageing. They generally combine compounds that support neuroprotection, neuronal signalling, brain lipid balance or the fight against oxidative stress.

Among the plants most frequently cited in the scientific literature are Ginkgo biloba and Bacopa monnieri, which contribute to normal blood circulation (which underpins the brain’s responsiveness), and Centella asiatica and Huperzia serrata, which support cognitive function (12–15).

-These plant extracts are combined in the Neurex™ blend, which also contains vitamins B9 and B12, as well as many other beneficial nutrients.

The brain is an organ particularly rich in structural lipids, notably DHA. This omega-3 fatty acid, a major component of neuronal membranes, helps maintain normal brain function (16). Hence the importance of ensuring an adequate daily intake.

-The Super DHA supplement, which also contains EPA, is formulated using sustainably sourced fish oil.

Brain phospholipids are also attracting growing interest in research into neurotransmission and brain ageing. In particular, phosphatidylserine, another key component of neuronal membranes, which binds to DHA at the synapses (17). Unfortunately, its synthesis declines with age.

-It is possible to take phosphatidylserine supplements, for example with PS100.

SUPERSMART ADVICE

References

  1. Jin U, Park SJ, Park SM. Cholesterol Metabolism in the Brain and Its Association with Parkinson's Disease. Exp Neurobiol. 2019 Oct 31;28(5):554-567. doi: 10.5607/en.2019.28.5.554. PMID: 31698548; PMCID: PMC6844833.
  2. Azarfar K, Decourt B, Sanchez Camacho B, Lawrence JJ, Omondi TR, Sabbagh MN. Cholesterol-modifying strategies for Alzheimer disease: promise or fallacy? Expert Rev Neurother. 2025 May;25(5):521-535. doi: 10.1080/14737175.2025.2483928. Epub 2025 Apr 3. PMID: 40140971; PMCID: PMC12068190.
  3. Hansen SB, Wang H. The shared role of cholesterol in neuronal and peripheral inflammation. Pharmacol Ther. 2023 Sep;249:108486. doi: 10.1016/j.pharmthera.2023.108486. Epub 2023 Jun 29. PMID: 37390970.
  4. Shin KC, Ali Moussa HY, Park Y. Cholesterol imbalance and neurotransmission defects in neurodegeneration. Exp Mol Med. 2024 Aug;56(8):1685-1690. doi: 10.1038/s12276-024-01273-4. Epub 2024 Aug 1. PMID: 39085348; PMCID: PMC11371908.
  5. Miramontes S, Khan U, Ferguson EL, Sirota M, Glymour MM. The association of cholesterol levels with memory and memory change over a 14-year period in a US national cohort. Alzheimers Dement (N Y). 2025 Jan 3;11(1):e70021. doi: 10.1002/trc2.70021. PMID: 39759951; PMCID: PMC11696025.
  6. Dias IH, Polidori MC, Griffiths HR. Hypercholesterolaemia-induced oxidative stress at the blood-brain barrier. Biochem Soc Trans. 2014 Aug;42(4):1001-5. doi: 10.1042/BST20140164. PMID: 25109993.
  7. Cicero AFG, Fogacci F, Banach M. Red Yeast Rice for Hypercholesterolemia. Methodist Debakey Cardiovasc J. 2019 Jul-Sep;15(3):192-199. doi: 10.14797/mdcj-15-3-192. PMID: 31687098; PMCID: PMC6822657.
  8. Bundy R, Walker AF, Middleton RW, Wallis C, Simpson HC. Artichoke leaf extract (Cynara scolymus) reduces plasma cholesterol in otherwise healthy hypercholesterolemic adults: a randomized, double blind placebo controlled trial. Phytomedicine. 2008 Sep;15(9):668-75. doi: 10.1016/j.phymed.2008.03.001. PMID: 18424099.
  9. Ismail N, Kureishy N, Church SJ, Scholefield M, Unwin RD, Xu J, Patassini S, Cooper GJS. Vitamin B5 (d-pantothenic acid) localizes in myelinated structures of the rat brain: Potential role for cerebral vitamin B5 stores in local myelin homeostasis. Biochem Biophys Res Commun. 2020 Jan 29;522(1):220-225. doi: 10.1016/j.bbrc.2019.11.052. Epub 2019 Nov 20. PMID: 31759626; PMCID: PMC6977085.
  10. Cheurfa M, Abdallah HH, Allem R, Noui A, Picot-Allain CMN, Mahomoodally F. Hypocholesterolaemic and antioxidant properties of Olea europaea L. leaves from Chlef province, Algeria using in vitro, in vivo and in silico approaches. Food Chem Toxicol. 2019 Jan;123:98-105. doi: 10.1016/j.fct.2018.10.002. Epub 2018 Oct 4. PMID: 30292622.
  11. Mansour HMM, Zeitoun AA, Abd-Rabou HS, El Enshasy HA, Dailin DJ, Zeitoun MAA, El-Sohaimy SA. Antioxidant and Anti-Diabetic Properties of Olive (Olea europaea) Leaf Extracts: In Vitro and In Vivo Evaluation. Antioxidants (Basel). 2023 Jun 14;12(6):1275. doi: 10.3390/antiox12061275. PMID: 37372005; PMCID: PMC10295535.
  12. Gościniak A, Stasiłowicz-Krzemień A, Szeląg M, Pawlak J, Skiera I, Kwiatkowska H, Nowak N, Bernady K, Trzaskoma P, Zimak-Krótkopad O, Cielecka-Piontek J. Bacopa monnieri: Preclinical and Clinical Evidence of Neuroactive Effects, Safety of Use and the Search for Improved Bioavailability. Nutrients. 2025 Jun 5;17(11):1939. doi: 10.3390/nu17111939. PMID: 40507208; PMCID: PMC12158153.
  13. Silberstein RB, Pipingas A, Song J, Camfield DA, Nathan PJ, Stough C. Examining brain-cognition effects of ginkgo biloba extract: brain activation in the left temporal and left prefrontal cortex in an object working memory task. Evid Based Complement Alternat Med. 2011;2011:164139. doi: 10.1155/2011/164139. Epub 2011 Aug 18. PMID: 21941584; PMCID: PMC3166615.
  14. Jiang J, Han R, Ren H, Yao Y, Jiang W. A review of neuroprotective properties of Centella asiatica (L.) Urb. and its therapeutic effects. Ann Med. 2025 Dec;57(1):2559122. doi: 10.1080/07853890.2025.2559122. Epub 2025 Sep 11. PMID: 40932246; PMCID: PMC12427517.
  15. Callizot N, Campanari ML, Rouvière L, Jacquemot G, Henriques A, Garayev E, Poindron P. Huperzia serrata Extract 'NSP01' With Neuroprotective Effects-Potential Synergies of Huperzine A and Polyphenols. Front Pharmacol. 2021 Aug 30;12:681532. doi: 10.3389/fphar.2021.681532. PMID: 34526893; PMCID: PMC8435632.
  16. Dighriri IM, Alsubaie AM, Hakami FM, Hamithi DM, Alshekh MM, Khobrani FA, Dalak FE, Hakami AA, Alsueaadi EH, Alsaawi LS, Alshammari SF, Alqahtani AS, Alawi IA, Aljuaid AA, Tawhari MQ. Effects of Omega-3 Polyunsaturated Fatty Acids on Brain Functions: A Systematic Review. Cureus. 2022 Oct 9;14(10):e30091. doi: 10.7759/cureus.30091. PMID: 36381743; PMCID: PMC9641984.
  17. Ma X, Li X, Wang W, Zhang M, Yang B, Miao Z. Phosphatidylserine, inflammation, and central nervous system diseases. Front Aging Neurosci. 2022 Aug 3;14:975176. doi: 10.3389/fnagi.2022.975176. PMID: 35992593; PMCID: PMC9382310.

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