Nicotine and Alzheimer's Disease: The Research

Alzheimer's disease strips the brain of nicotinic acetylcholine receptors early, and nicotine has been tested both in the laboratory against amyloid and in human trials of mild cognitive impairment. This page collects the published research on nicotine and Alzheimer's disease, each paper summarised in plain language with its PubMed record.

This collection is research only: papers found on PubMed, each described as its own abstract reports it. Cell and animal results are labelled as such, and harms are listed beside benefits. It is not medical advice.

Table of Contents

  1. The Papers
  2. PubMed Topic Searches
  3. Connections
  4. Featured Videos

The Papers (22)

Newest first. Study types on this page — Review: 13 · Animal study: 3 · Cell study: 5 · Other: 1. Each summary is written from the paper’s own abstract; follow the PubMed link for the full record.

Meta-Analysis on Nicotine's Modulation of HIV-Associated Dementia

Other, 2022. This was a computer-based analysis, not a study in people or animals. Researchers used a pathway-analysis software tool and its database of published findings to map how nicotine-related molecules might connect to five molecules linked to HIV-associated dementia, a brain condition that affects many people living with HIV. They found 29 molecules in between. The tool predicted that nicotine would switch on the dementia-linked molecules, which would make the condition worse. However, other pathway models suggested that nicotine given together with drugs that block certain of those in-between molecules might lower the dementia-linked molecules, so the authors propose nicotine may have protective potential that would need to be tested.

Krishnan V, Vigorito M, Kota NK et al. (2022). Meta-Analysis on Nicotine's Modulation of HIV-Associated Dementia. J Neuroimmune Pharmacol. — PubMed PMID: 34757527 · doi:10.1007/s11481-021-10027-2

Nicotine prevents in vivo Aβ toxicity in Caenorhabditis elegans via SKN-1

Animal study, 2021. This study used tiny worms (C. elegans) that were genetically changed to make amyloid-beta, the protein that builds up in Alzheimer's disease. In these worms, nicotine at 5 μM reduced the paralysis caused by amyloid-beta, lowered amyloid-beta deposits and clumps, and reduced harmful reactive oxygen species. In a lab dish, nicotine did not stop amyloid-beta from clumping. In the worms, the protective effect depended on a stress-defence pathway called SKN-1: when that pathway was blocked, nicotine no longer prevented the paralysis. These results come only from worms, not from people.

Lu X, Zhang Y, Li H et al. (2021). Nicotine prevents in vivo Aβ toxicity in Caenorhabditis elegans via SKN-1. Neurosci Lett. — PubMed PMID: 34274434 · doi:10.1016/j.neulet.2021.136114

Nicotine Promotes AβPP Nonamyloidogenic Processing via RACK1-Dependent Activation of PKC in SH-SY5Y-AβPP695 Cells

Cell study, 2020. This lab study used human nerve-like cells grown in dishes. The cells were engineered to make a mutant form of the amyloid precursor protein, the protein that is cut into the amyloid-beta pieces that build up in Alzheimer's disease. After 6 hours of nicotine exposure, the cells made more of the enzyme ADAM10 and more of the harmless C83 fragment, and the effect grew with the dose. The pathway that produces amyloid-beta, including Aβ40 and Aβ42 levels, did not change. Nicotine worked through the PKC enzyme and its helper protein RACK1: blocking PKC or lowering RACK1 stopped the effect. The authors suggest nicotine could be a potential molecule for Alzheimer's treatment, but this result comes only from cells.

He W, Tu M, Du Y et al. (2020). Nicotine Promotes AβPP Nonamyloidogenic Processing via RACK1-Dependent Activation of PKC in SH-SY5Y-AβPP695 Cells. J Alzheimers Dis. — PubMed PMID: 32250310 · doi:10.3233/JAD-200003

Chronic memantine decreases nicotine self-administration in rats

Animal study, 2019. This study in adult female rats tested whether memantine, an Alzheimer's drug that blocks NMDA glutamate receptors in the brain, changes how much nicotine the rats choose to give themselves. A single dose of memantine slightly but significantly increased nicotine self-administration, and the effect grew with the dose. Daily treatment had the opposite effect: from the second week, memantine-treated rats took significantly less nicotine than untreated rats, whose intake kept rising, and the lower intake lasted through the week after treatment stopped. The authors suggest that drugs acting on NMDA glutamate receptors may help people quit smoking, but these results come only from rats.

Levin ED, Wells C, Yao L et al. (2019). Chronic memantine decreases nicotine self-administration in rats. Eur J Pharmacol. — PubMed PMID: 31421087 · doi:10.1016/j.ejphar.2019.172592

Age- and Nicotine-Associated Gene Expression Changes in the Hippocampus of APP/PS1 Mice

Animal study, 2019. This study used mice bred to develop Alzheimer's-like brain changes. Researchers compared gene activity in the hippocampus, a memory area of the brain, in 18-month-old and 7-month-old mice, and also looked at how nicotine treatment changed gene activity at each age. The older mice had higher activity in genes linked to calcium overload, immune response and nerve-cell connections, including 14 types of calcium channel, and lower activity in genes linked to energy production and metabolism. Nicotine changed different genes at different ages: in young mice it increased fat-related metabolism and reduced certain cell-signaling pathways, while in old mice it affected genes tied to cell aging and death, and the authors suggest that extra nicotinic stimulation might not help in late-stage disease. These results come from mice only.

Yang J, Long Y, Xu DM et al. (2019). Age- and Nicotine-Associated Gene Expression Changes in the Hippocampus of APP/PS1 Mice. J Mol Neurosci. — PubMed PMID: 31399937 · doi:10.1007/s12031-019-01389-7

Modulatory Effects of Nicotine on neuroHIV/neuroAIDS

Review, 2018. This review looks at how nicotine, which acts on nicotinic acetylcholine receptors in the brain, may affect the memory and thinking problems linked to HIV infection (HIV-associated neurocognitive disorders), which remain common even with modern antiretroviral treatment. The authors summarise earlier animal and cell studies, including work in a rat model engineered to carry HIV genes, which suggested that nicotine may protect nerve cells, possibly by reducing inflammation, similar to effects seen in Alzheimer's and Parkinson's disease research. They stress that tobacco smoking is harmful, including in people with HIV, and conclude that more research is needed on nicotine's dual effects to see whether nicotine or related compounds could be used medically in a purer, less dangerous form.

Han H, Yang Z, Chang SL et al. (2018). Modulatory Effects of Nicotine on neuroHIV/neuroAIDS. J Neuroimmune Pharmacol. — PubMed PMID: 30215204 · doi:10.1007/s11481-018-9806-5

Nicotine slows down oligomerisation of α-synuclein and ameliorates cytotoxicity in a yeast model of Parkinson's disease

Cell study, 2017. Researchers tested nicotine on alpha-synuclein, a protein that clumps together in the brain cells of people with Parkinson's disease, using test-tube experiments and yeast cells. Nicotine slowed the clumping and reduced the buildup of small protein clusters thought to be the most toxic form. In a dose-dependent way, this lowered oxidative stress, reduced cell damage and improved yeast cell survival. Nicotine appeared to bind the protein briefly and change its shape. These results come only from laboratory and yeast experiments, not from animals or people.

Kardani J, Sethi R, Roy I (2017). Nicotine slows down oligomerisation of α-synuclein and ameliorates cytotoxicity in a yeast model of Parkinson's disease. Biochim Biophys Acta Mol Basis Dis. — PubMed PMID: 28167231 · doi:10.1016/j.bbadis.2017.02.002

Application of nicotine enantiomers, derivatives and analogues in therapy of neurodegenerative disorders

Review, 2007. This review looks at how nicotine and closely related compounds have been studied as possible treatments for several brain and nervous-system conditions, including Alzheimer's disease, Parkinson's disease, Tourette's syndrome and schizophrenia. It also covers how nicotine is measured and extracted in the laboratory, how it acts on the body at the molecular level, and natural and synthetic nicotine-like compounds being considered for medical use. The authors compare the two mirror-image forms of nicotine found in nature and suggest that the less common form, (R)-nicotine, which they describe as less toxic, may have a place in medicine.

Pogocki D, Ruman T, Danilczuk M et al. (2007). Application of nicotine enantiomers, derivatives and analogues in therapy of neurodegenerative disorders. Eur J Pharmacol. — PubMed PMID: 17376429 · doi:10.1016/j.ejphar.2007.02.038

Effects of nicotinic stimulation on cognitive performance

Review, 2004. This review looks at human studies of how nicotine and similar drugs that act on nicotinic receptors in the brain affect thinking and memory. Across these studies, attention was the mental skill most likely to improve when these receptors were stimulated. In people with Alzheimer's disease, Parkinson's disease, attention deficit/hyperactivity disorder or schizophrenia, the studies suggest nicotinic drugs could be useful as treatments, but in healthy non-smokers nicotine tended to make performance worse. The authors explain this difference by each person's starting level of brain function: healthy people are unlikely to benefit except on very demanding tasks, while people with these conditions can benefit.

Newhouse PA, Potter A, Singh A (2004). Effects of nicotinic stimulation on cognitive performance. Curr Opin Pharmacol. — PubMed PMID: 15018837 · doi:10.1016/j.coph.2003.11.001

Nicotine and nicotinic receptor involvement in neuropsychiatric disorders

Review, 2004. This review looks at experimental and clinical research on nicotine and nicotinic receptors, the brain receptors that nicotine acts on, in several brain and mental health conditions. The authors say changes in the number or function of these receptors have been linked to Alzheimer's disease for several years. They describe growing evidence that the receptors may also play an important role in schizophrenia, Parkinson's disease, anxiety disorders and attention deficit-hyperactivity disorder (ADHD). The review aims to identify targets for developing new medicines.

Newhouse P, Singh A, Potter A (2004). Nicotine and nicotinic receptor involvement in neuropsychiatric disorders. Curr Top Med Chem. — PubMed PMID: 14754447 · doi:10.2174/1568026043451401

Nicotine and neurodegeneration in ageing

Review, 2002. This review looks at how the brain's nicotinic receptors (the receptors nicotine acts on) relate to ageing and dementia. It reports that people with dementia consistently show a marked loss of nicotine binding sites in parts of the brain, which is thought to contribute to memory and thinking problems. The review describes laboratory and animal work, in living animals and in cultured nerve cells, in which nicotine protected nerve cells from damage caused by overactive excitatory chemicals and by beta-amyloid, the main protein in the plaques found in Alzheimer's disease. It also notes that studies of genetically altered animals lacking certain nicotinic receptor types are helping explain how nicotine can both protect nerve cells and harm them.

Zanardi A, Leo G, Biagini G et al. (2002). Nicotine and neurodegeneration in ageing. Toxicol Lett. — PubMed PMID: 12052660 · doi:10.1016/s0378-4274(01)00502-1

Cognitive effects of nicotine

Review, 2001. This review looks at research on how nicotine and other substances that act on nicotinic receptors affect thinking skills. The authors report that nicotine has been found to improve performance on attention and memory tasks. They also report that clinical studies using nicotine skin patches showed benefits for thinking problems linked to Alzheimer's disease, schizophrenia and attention-deficit/hyperactivity disorder (ADHD). In animal studies, the improvement in working memory lasted with long-term exposure, and two types of nicotinic receptors in the hippocampus, a memory area of the brain, were found to be key to these effects.

Rezvani AH, Levin ED (2001). Cognitive effects of nicotine. Biol Psychiatry. — PubMed PMID: 11230877 · doi:10.1016/s0006-3223(00)01094-5

Nicotine and brain disorders

Review, 2000. This review looks at the nicotinic receptors in the brain, the docking sites that nicotine acts on. It explains that these receptors matter for memory and thinking, and that they play a part in several brain disorders: Parkinson's disease, Alzheimer's disease, Tourette's syndrome, schizophrenia, depression and attention deficit disorder. The authors write that clinical studies of these same conditions found nicotine had beneficial effects, both as a treatment and as a way to help prevent them. It is a summary of earlier research, not a new study, and the abstract gives no patient numbers.

Mihailescu S, Drucker-Colín R (2000). Nicotine and brain disorders. Acta Pharmacol Sin. — PubMed PMID: 11263271

Nicotine for Alzheimer's disease

Review, 2000. This systematic review looked for high-quality, placebo-controlled trials testing nicotine, given by skin patch or into a vein for more than a day, in people with Alzheimer's disease. No trials met the standard for inclusion, so no results could be combined, and the trials that were looked at were of poor quality. Their data fit equally well with nicotine causing harm, making no difference, or helping. The authors concluded the review could not give reliable evidence that nicotine is a useful treatment for Alzheimer's disease, and they noted nicotine's serious side effects, especially heart and blood-vessel risks in older people and effects on sleep and behavior.

López-Arrieta JM, Rodríguez JL, Sanz F (2000). Nicotine for Alzheimer's disease. Cochrane Database Syst Rev. — PubMed PMID: 10796667 · doi:10.1002/14651858.CD001749

Nicotinic stimulation produces multiple forms of increased glutamatergic synaptic transmission

Cell study, 1998. This laboratory study looked at nerve cells in the hippocampus, a brain area important for learning and memory that carries many nicotinic receptors. Strong, brief activation of these receptors increased signalling through glutamate, one of the brain's main messenger chemicals. One form of the boost lasted only seconds, and another lasted for minutes after the activating drug had been washed away. The effect needed calcium outside the cells and worked through alpha7-type nicotinic receptors on the nerve endings that release glutamate. The authors suggest this may be one way nicotinic activity affects thinking, and that losing these mechanisms may add to the memory problems of Alzheimer's disease. The work was done on isolated brain tissue, not in living people.

Radcliffe KA, Dani JA (1998). Nicotinic stimulation produces multiple forms of increased glutamatergic synaptic transmission. J Neurosci. — PubMed PMID: 9736631 · doi:10.1523/JNEUROSCI.18-18-07075.1998

Nicotinic receptor stimulation protects neurons against beta-amyloid toxicity

Cell study, 1997. Researchers grew rat brain nerve cells in the lab and exposed them to beta-amyloid, a protein fragment that builds up in the brains of people with Alzheimer's disease and damages nerve cells. Adding nicotine at the same time greatly reduced the number of cells that died, and a higher nicotine dose gave more protection. This protection went away when drugs that block nicotinic receptors were added, including a blocker of the alpha7 receptor type, and a drug that switches on only alpha7 receptors also protected the cells. The authors suggest that switching on alpha7 nicotinic receptors may help shield nerve cells from beta-amyloid damage, but these results come from cells in a dish, not from animals or people.

Kihara T, Shimohama S, Sawada H et al. (1997). Nicotinic receptor stimulation protects neurons against beta-amyloid toxicity. Ann Neurol. — PubMed PMID: 9266724 · doi:10.1002/ana.410420205

Does nicotine have beneficial effects in the treatment of certain diseases?

Review, 1996. This 1996 review looks at why smokers seem less likely to develop ulcerative colitis, Alzheimer's disease and Parkinson's disease, and suggests that nicotine itself may be responsible for this effect. The author explains that nicotine acts on nicotinic receptors in the brain, which are reduced in Alzheimer's and Parkinson's disease, and that these receptors also affect dopamine, a brain chemical involved in Parkinson's disease and Tourette's syndrome. The review says pure nicotine has no known cancer-causing properties and can be given through skin patches or tablets, but it also notes that nicotine has many harmful side effects and that no one should be encouraged to smoke. It concludes that nicotine may have some medical value, or at least may be useful for developing future drugs.

Birtwistle J, Hall K (1996). Does nicotine have beneficial effects in the treatment of certain diseases?. Br J Nurs. — PubMed PMID: 9006184 · doi:10.12968/bjon.1996.5.19.1195

Hippocampal synaptic transmission enhanced by low concentrations of nicotine

Cell study, 1996. This laboratory study looked at whether nicotine acts on nicotinic receptors in the hippocampus, a brain area important for learning and memory. By measuring calcium inside single nerve endings in hippocampal tissue, the researchers found that low concentrations of nicotine, acting on receptors that contain the alpha7 subunit, let in enough calcium to trigger the release of chemical messengers and strengthen signals between nerve cells. The work was done on brain tissue in the lab, not in people. The authors suggest this may be one way nicotine affects thinking and memory, and that losing this signalling could help explain memory problems in Alzheimer's disease.

Gray R, Rajan AS, Radcliffe KA et al. (1996). Hippocampal synaptic transmission enhanced by low concentrations of nicotine. Nature. — PubMed PMID: 8878480 · doi:10.1038/383713a0

Pharmacology of nicotine: addiction and therapeutics

Review, 1996. This review describes how nicotine works in the body, both as the substance that keeps people addicted to tobacco and as a medicine to help people quit smoking. Nicotine acts on nicotinic receptors in the nervous system, and its effects depend on how fast and by what route it is taken and on tolerance; a few people have been described who break down nicotine unusually slowly and make little cotinine. The authors note that nicotine affects most organ systems, but its contribution to smoking-related disease is still unclear. At the time, nicotine medicines were available as a gum, a skin patch and a nasal spray for quitting smoking, and nicotine was being studied for ulcerative colitis, Alzheimer's disease, Parkinson's disease, Tourette's syndrome, sleep apnea and attention deficit disorder.

Benowitz NL (1996). Pharmacology of nicotine: addiction and therapeutics. Annu Rev Pharmacol Toxicol. — PubMed PMID: 8725403 · doi:10.1146/annurev.pa.36.040196.003121

Nicotine as a therapeutic drug

Review, 1995. This review looks at whether nicotine itself could be used as a medicine. It finds the strongest evidence is for ulcerative colitis. Whether nicotine helps in Parkinson's or Alzheimer's disease is still unclear, and the authors say more research is needed, including on how safe and well tolerated it is in these diseases. They say nicotine treatment should for now be tried only inside research studies, that no form of tobacco should be used to deliver nicotine, and they urge everyone who uses tobacco to quit.

Westman EC, Levin ED, Rose JE (1995). Nicotine as a therapeutic drug. N C Med J. — PubMed PMID: 7862206

Nicotine as a cognitive enhancer

Review, 1992. This 1992 review looks at research on whether nicotine affects thinking skills. The authors report that in healthy volunteers, nicotine improved attention on many kinds of tasks and improved both short-term and longer-term memory. They also report that it improved attention in patients with probable Alzheimer's disease. Some of the memory effects may come from better attention, but others appear to come from the brain storing new memories more firmly, because nicotine still helped when it was given after the learning task.

Warburton DM (1992). Nicotine as a cognitive enhancer. Prog Neuropsychopharmacol Biol Psychiatry. — PubMed PMID: 1579636 · doi:10.1016/0278-5846(92)90069-q

Beneficial effects of nicotine

Review, 1991. This 1991 review looks at what pure nicotine, apart from tobacco, does in the body. Nicotine attaches to nicotinic receptors throughout the body, which triggers the release of several brain chemical messengers, especially catecholamines and serotonin. The author lists possible effects of long-term use: reinforcing effects that can drive continued use, lower body weight, better performance, and possible protection against Parkinson's disease, Tourette's disease, Alzheimer's disease, ulcerative colitis and sleep apnea. The paper notes that nicotine in tobacco causes illness and death in millions of people, that these effects vary greatly in how reliable they are, and that this justifies further research into possible medical uses.

Jarvik ME (1991). Beneficial effects of nicotine. Br J Addict. — PubMed PMID: 1859921 · doi:10.1111/j.1360-0443.1991.tb01810.x

Back to Table of Contents

PubMed Topic Searches

  1. PubMed: Alzheimer's Disease and nicotine (the search this page is built from)

Back to Table of Contents

Connections

Back to Table of Contents