Opposites Attract: Cancer and Alzheimer’s Disease

Cancer and Alzheimer’s Are Inversely Correlated

Biomarkers in cancer and Alzheimer’s seem to be opposites. Let’s delve into why.


  1. Basics
  2. P53
  3. Estrogen
  4. Neurotrophins
  5. Growth Factors
  6. cAMP
  7. EGFR
  8. BCL-2
  9. Insulin
  10. Cell Proliferation
  11. HSV
  12. TDP-43
  13. APOE
  14. NCAM (CD56)
  15. TNF-α
  16. PI3K, AKT, and mTOR
  17. Telomerase
  18. ROS
  19. ACE
  20. HHT
  21. Vimentin
  22. Carbonic Anhydrases (CA)
  23. Carnosine
  24. Ubiquitin
  25. SAPK
  26. Vitamin E
  27. FOXO
  28. GSK3
  29. C-ABL
  30. IL-6
  31. S100B
  32. Tau Tangles
  33. More Research


If you are having trouble reading this, just read the bold parts in the sections below. 😊

Here is a brief summary:

  • Higher in Cancer/Lower in Alzheimer’s
    • P53
    • Estrogen
    • Neurotrophic Factors
    • Growth Factors
    • Cyclic Amp (cAMP)
    • EGFR
    • BCL-2
    • NCAM
    • PI3K, AKT, and mTOR
    • CA (Carbonic Anhydrases)
    • Insulin and like growth factors
    • CDK6
    • Telomerase
    • Ubiquitin
    • APOE
  • Higher in Alzheimer’s/Lower in Cancer
    • HSV (if you are infected)
    • ROS
    • HTT Protein (mutation)
    • Cell Death
    • Stress-activated protein kinases (SAPK)
    • GSK3
    • TNF-a
    • IL-6
    • Hyperphosphorylated tau
  • What You Want To Do


Here is a brief technical summary:

  • p53 is upregulated in Alzheimer’s disease and down-regulated in Cancer
  • Estrogen is neuroprotective but increases the risk of cancers
  • Neurotrophins and growth factors are neuroprotective but are also involved in tumor growth progression
  • Age-related decline in the proliferation of new cells contribute to AD development while pathways and mechanisms that contribute to growth and proliferation delays AD
  • cAMP provides a survival signal for neurons and is also involved in tumor progression
  • EGFR is overexpressed in cancer but EGFR is not found in Alzheimer’s plaques
  • Bcl-2 downregulated in Alzheimer’s disease but is overexpressed in cancer
  • Apoptosis pathways are upregulated in Alzheimer’s disease but downregulated in cancer
  • IGF-1 is decreased in Alzheimer’s disease but increased in cancer, the dysfunctional proliferation of neurons occurs in Alzheimer’s but in cancer, there is over-proliferation of cells
  • HSV is oncolytic but contributes to Alzheimer’s disease development
  • TDP-43 role in Alzheimer’s disease and cancer and its relation to IGF signifies the inverse relationship between cancer and AD
  • Alzheimer’s risk decreases from apoE4 to E3 to E2 but growth and survival improves respectively
  • Pathophysiologic notch signals potentially contribute to cancer but presenilins are also involved in notch signaling and they mutate in familial early-onset AD
  • Neural cell adhesion molecules decrease in AD but stain positive in neoplasia.
  • TNF-α has anti-cancer properties and its overexpression causes neurotoxic environment but the secondary signal is necessary for the induction of neuronal death
  • PI3K/AKT/mTOR pathway is neuroprotective but in many cancers this pathway is overactive
  • Telomerase in cancer cells prevents senescence-related death and AD is associated with accelerated neuronal death
  • ROS when excessive slows cancer proliferation and ROS are increased in Alzheimer’s disease
  • ACE levels are decreased in Cancer but are elevated in Alzheimer’s disease


TP53 (P53) is downregulated in most tumors. R

Inactivation of TP53, predisposes you to cancer, while activation of TP53 in common in AD. R

P53 can initiate apoptosis if DNA damage is unable to be repaired. R

P53 activation leads to cell cycle arrest via p21. Upregulation of p21 results in aging and cell cycle arrest. R

Amyloid Precursor Protein (APP) mediates part of p53 expression. Aβ binds to p53 and tau phosphorylation is indirectly stimulated by p53. R

Complete deletion of Tp53 increases lifetime cancer risk increases to 100% by age 70 years in patients with Li-Fraumeni syndrome. R

P53 plays a role in driving insulin resistance in Alzheimer’s. R

Upregulation of P53 is present in AD and its downregulation or deletion is involved in cancers.


Estrogen is both neurotrophic and neuroprotective. R

It even protects isolated neurons from hypoglycemic and ischemic injuries, oxidative stress, and Aβ damage . R

Estrogen also increases nerve growth factor production (such as BDNF, NGF, GDNFCNTF, CDNF and MANF). R

Nerve growth factors promote neuronal viability, repair and growth of damaged neurons, and dendritic branching. R

Estrogen reduces the risk of AD. R

Estrogen increases the risk of cancers (such as ovarian, endometrial, and breast). R


NGF (nerve growth factor) regulates and promotes cancer. R

BDNF (brain-derived nerve growth factor) occurs in colon cancer. R

EGF, NGF, BDNF, NT-3, NT-4/5, EGFR, trk A, trk B, and trk C play a role in prostate cancer pathogenesis. R

Glutamate and neurotrophic factors are regulated in developmental and adult neuroplasticity. R

Neurotrophic factors are downregulated in AD but upregulated in cancer. 

Growth Factors

TGF-β (trans-human growth factor beta) halts cell cycle at the G1 stage to stop proliferation and promotes cells to differentiate/go towards self-destruction. R

In many cancer cells, TGF-β is mutated and its normal functioning is impaired. R

It contributes to making cancer more aggressive causing immunosuppression and angiogenesis. R

TGF-β also converts effector T-cells into suppressor T-cells, which halts the inflammatory reaction. R

TGF-β is increased in the cerebrospinal fluid and blood of Alzheimer’s patients, compared to control subjects. R

TGF-β is lower in cancer and higher in AD. 


Cyclic AMP (cAMP) is a survival signal for neurons. R

It become significantly enhanced when combined with trophic factors such as  BDNF, CNTF, FGF, GDNF, and HGF. R

Cyclic AMP gene activation and deregulation are linked to the growth of some cancers. R


Epidermal growth factor receptor (EGFR) is over-expressed in many cancers. R

EGF plays a role in hippocampal neurogenesis and cognitive function. R

EGFR is absent in Alzheimer’s plaques. R


BCL-2 regulates cell death. R

It is overexpressed in many cancers.  R

It is most commonly associated with resistance to chemotherapy and radiotherapy. R

When BCL-2 is expressed, cancer cells are less likely to self destruct. R

BCL-2 has been shown to provide protection against Aβ plaque cell death (possibly related to the decrease in beta amyloid-induced activation of p38 MAPK and NF-κB). R

BCL-2 is increased in cancer, but in Alzheimer’s, it is down-regulatedR


Low insulin or insulin-like growth factors (IGF) can potentiate Alzheimer’s and dementia. R

IGF levels are high in cancer. R

IGF-1 plays an important role in promoting cancer. It inhibits cell death and promotes growth.

It also is involved with neurogenesis, myelination, synaptogenesis, and dendritic branching. R

High levels of IGF-1 have been associated with a higher IQ. R

IGF-2 is more important for the development and function of the liver, kidney, and brain. R

Birth defects in producing IGF-1 protects against developing cancer. R

Here is a list of ways to increase or decrease IGF-1.

In diabetic mice, cognitive impairment was associated with mitochondrial effects from AB presence. Insulin and CoQ10 treatment fixed this. R

It is known that type 2 diabetics have a higher chance of developing Alzheimer’s and dementia. R

Intranasal Insulin has been shown to be beneficial for Alzheimer’s patients with type 3 diabetes. R

Cell Proliferation

Cell proliferation (cell growth) is inversely dysfunctional in both Alzheimer’s and cancer.

In Alzheimer’s, cells die too quicklyR

In cancer, cells don’t die. R

Learning how to activate the endocannabinoid (eCB) system can help with cell proliferation. R

The immune system plays a role in neurogenesis and is based on neurotrophins, cytokines, hormones, neurotransmitter systems, and growth factors. R

For example, neurogenesis has the potential to delay or halt AD-linked cognitive decline. R

TGFb-1 enhances neurogenesis in Alzheimer’s patients. R

See here how to increase TGFb-1, NGF and BDNF.


Herpes Simplex Virus (HSV) 1 damages DNA (specifically in GADD3). R

HSV1 DNA has been found in Alzheimer’s disease AB plaques. R

Interestingly, HSV1 leads to an increase in AB plaques, but lower APP levels (the precursor). R

HSV1 is oncolytic, which means it contributes to cancer cell death. R

Thus, HSV1 kills cancer cells but may contribute to AB plaques in Alzheimer’sR


TAR DNA-binding protein 43 (TDP-43) is a protein involved in cancer, Alzheimer’s, ALS, HIV, AIDS, and TBI. R

In normal circumstances, TDP-43 regulates CDK6.

CDK6 is upregulated in cancer and downregulated in Alzheimer’s.

Part of Alzheimer’s pathology is an abnormality in TDP-43. This causes gene expression problems and increased cell death. R

Abnormalities can also create cell death in hippocampus and cognitive impairment. R R

Elevated levels of CDK6 are associated with several tumors. R

TDP-43 abnormalities can be potentiated by IGF deficiency. R

Treatment of IGF and CoQ10 can prevent mitochondrial impairment from AB related oxidative stress. R


Apolipoprotein E (APOE) is a gene and protein very commonly associated with Alzheimer’s. R

Apolipoprotein E combines with fats (lipids) in the body to form molecules called lipoproteins.R

Lipoproteins are responsible for packaging cholesterol and other fats and carrying them through the bloodstream. R

There are 3 alleles in the APOE gene. R

People who inherit one copy of the APOE4 allele have an increased chance of developing Alzheimer’s and those who inherit two copies of the allele are at even greater risk since they have less APOE. R

APOE4 contributes to reduced neurite outgrowth. R

APOE3 posses less of a risk compared to E4. R

E3 also inhibits tumor cell growth and increases neurite outgrowthR

E2 is rare and the least dangerousR

Interestingly, E2 and E4 have opposite actions. R

A high-fat diet has been shown to increase APOE. R

APOE also plays a role in tissue repair, cell growth, and immune regulation. R

It helps with maintenance and cell duplication of neural stem cells. R

APOE is able to restore neuronal function after injury, but APOE4 is unable to do this properly. R 


APOE4 is associated with lower NCAM (neural cell adhesion molecule, also called CD56) levels. R

Alzheimer’s is also associated with lower BDNF levels in the temporal and frontal brain regions. R

Since NCAM is involved with inducing neurite outgrowth (via GFGR), it acts on other signal pathways. R

NCAM is used to identify some types of tumors. R

AB plaques can harm NCAM2 and there seem to be less NCAM2 levels in the hippocampus in Alzheimer’s. R

NCAM is higher in cancer and lower in Alzheimer’s.


Tumor Necrosis Factor Alpha is overexpressed in Alzheimer’s. R

TNF-α over-expression has been shown to: R

  • decrease branching of dendrites
  • antagonize the production of NGF
  • lower neurotrophin levels in hippocampal region

TNF-α overexpression is associated with memory impairment and learning function in hippocampus. R

TNF-a inhibitions has been shown to improve cognitive status in Alzheimer’s patients. R

When TNF-a is expressed alone, it has been shown to protect against neurotoxicity, even AB plaque. This means the detrimental effects may be cause when combined with secondary signals, such as endogenous or exogenous stimuli. R


Activation of PI3K can activate AKT. R

AKT is invovled in angiogenesis, cell cycling, metabolism, cell survival, and neuroprotection. R

It also regulates cell death. R

The PI3K/AKT/MTOR pathway is very neuroprotective, but it can also halt cell death, which is bad in cancer. R

Thus, PI3K is higher in cancer, but lower in Alzheimer’s.


Telomerase replaces telomere loss during cell division. This helps prevent senescene and allows for an infinite amount of cell dividing. R

In cancer, telomerase is over-expressed. R

This causes too much telomere lengthening. R

On the other hand, shortening telomeres creates genetic instability and tumor formation. R

In Alzheimer’s, changes to gene expression impact chromatin and DNA. R

Changes in chromatin remodeling, including methylation and histone acetylation problems are involved in APP transcription. R R


During aging, reactive oxygen species (ROS) increases in the brain Alzheimer’s patients. R

It also accelerates with the progression of Alzheimer’s. R

ROS has been show to kill cancer cells. R

ROS may contribute to Alzheimer’s and be beneficial in cancer.


Angiotensin-Converting Enzyme (ACE) helps control blood pressure. R

ACE levels appear to be decreased in cancer, but elevated in Alzheimer’s (esp. in the cerebral cortex). R R


The huntingtin gene, also called the HTT or HD (Huntington disease gene), creates huntingtin protein. R

Huntington’s Disease is an inherited disorder that results in brain cell death. R

HTT plays a role in transporting materials, chemical signaling, and prevents apoptosis. R

It also influences many transcription factors and genes, such as BDNF. R

For example, normally HTT will upregulate BDNF transcription, but when HTT is mutated in Huntington disease, it downregulates the production of BDNF. R

In Huntington disease, HTT is modified and increases the rate of apoptosis and protects against cancer.  R

Normal HTT protein may prevent Alzheimers, but mutated (down-regulated) HTT may prevent cancer.


Vimentin is a protein that is the major cytoskeletal component of mesenchymal cells. R

In Alzheimer’s, MS, Pick’s Disease, ALS, and Cerebral Infarction patients, Vimentin-immunoreactivity is activated in astrocytes, macrophages, and microglia. In Alzheimer’s, they are specifically associated with AB plaques. R

Vimentin expression is used to counter neuronal damage. R

It also helps establish connections between synapses and dendrites. R

This is useful for learning and the formation of new memories. R

Vimentin also protects against cellular stress. R

Vimentin is a Intermediate Filament (IF) protein. R

IF proteins bring RNA and DNA-mediated events inside the cell nucleus. R

The over-expression of IF is correlated with upregulated tumor growth and invasion. R

Vimentin has decreased expression in Alzheimer’s disease but over-expression in cancer.

Carbonic Anhydrases

The activity of Carbonic Anhydrase (CA) is decreased in Alzheimer’s patient’s brains. R

Using CA activators, improves learning in animals with Alzheimer’s. R

CA is increased in cancer. R

CA is lower in Alzheimer’s, higher in cancer. 

CA is activated by carnosine. R


Carnosine lowers with age, which contributes to both cancer and Alzheimer’s. R

It is both neuroprotective and anti-cancer (anti-proliferative). R

Also, it has been found to be anti-aging. R

Carnosine can induce both cell death and cell survival. R

Toxicity from AB cells can be suppressed by carnosine. R

It also inhibits ROS. R

In Alzheimer’s, one of the first symptoms is usually a decline in the olfactory nerve. Carnosine, with the addition of Zinc, may prevent this. R

Carnosine is able to decrease the growth of tumors. R

It can help maintain normal levels of glutathione in the brain after stroke. R

Carnosine upregulates NOS and heat shock proteins (HSPs). R

HSPs induces expression HSF1, which can modify carcinogenesis and counter Alzheimer’s related damage. R R

This is the type of carnosine I take


Ubiquitin is a regulatory protein. It marks proteins for degradation. R

It is also similar to heat shock proteins. R

Ubiquitination regulates p53 and Myc. R

Ubiquitin protects APP (amyloid precursor protein) from becoming deformed. R

It also is neuroprotective during a stroke. R

Ubiquitin levels are decreased in Alzheimer’s and increased in cancer.


Stress-activated protein kinases (SAPK) regulate mitochondrial pathways (Bcl2 and p53). They play roles in cell death. R

SAPK upregulates p53 levels, whereas MAPK, p38, and JNKs inhibit SAPK and cell death. R

SAPK is downregulated in cancer and upregulated in Alzheimer’s. R

Vitamin E

Vitamin E regulates gene expression and signal transduction. R

It can decrease cognitive decline in high doses in Alzheimer’s patients. R


FOXO and carnosine have an interesting relationship in cancer and Alzheimer’s.

FOXO is important for counteracting stress, maintaining stem cell function, and longevity. R

Unfortunately, aging weakens the ability for the FOXO gene to function properly. This contributes to the development of Alzheimer’s. R

This upregulates p53, accelerating Alzheimer’s. R

Learn how to improve and activate the FOXO pathway. 


Glycogen synthase kinase (GSK) is encoded by two genes GSK-3 alpha (GSK3A) and GSK-3 beta (GSK3B). R

GSK-3 is implicated in a number of diseases, including Type II diabetes, Alzheimer’s Disease, inflammation, cancer, and bipolar disorder. R

MDM2 degrades p53, but in times of stress, p53 stabilizes with GSK3B causing hyperphosphorylated tau. R

GSK signaling contributes to the development of neurons, axonal growth, and brain development. R R

If GSK3 signaling is disrupted, then it can cause neurodevelopmental disorders, like Alzheimer’s. R


C-ABL is a protein that plays a role in the cell cycle. It turns on the cell cycle in the brain. R

Damage to this causes tau tangles. R

C-ABL is also present in AB plaques and is upregulated in Chronic Myeloid Leukemia (CML). R


Interleukin (IL-6), a marker for neuro-inflammation, is found in brains of Alzheimer’s and Down Syndrome. R

IL-6 is involved in the cellular cycle. R

Estrogen is an inhibitor of IL-6. R


S100B regulates cell and axonal death, among other cellular processes. R

It is also a signal for neurotrophic factors. R

S100B and its receptor are upregulated in Alzheimer’s. R

S100B is utilized for neural growth and maintenance, but unfortunately, it is insufficient to stop the progression of AD damage. R

Tau Tangles

Tau phosphorylation is essential for hippocampal growth. R

When tau becomes hyperphosphorylated, they cause microtubules to collapse in the brain. R

Hyperphosphorylated tau accumulates in the cerebral cortex and hippocampus in Alzheimer’s patients. R

Alzheimer’s is associated with hyperphosphorylated tau. R

More Research

  • APOE4 reduces hippocampal volume in AD and MS. R
  • Reduced levels of androgens also potentially increase the risk of AD. R
  • Detailed recognition of the role of p53/miRs crosstalk in driving insulin resistance in AD brains could improve the disease diagnostics and aid future therapy. R