Does HIV Make the Brain Old Before Its Time?

Approximately 10% of HIV-positive individuals develop profound memory loss, cognitive problems and severe depression. This HIV-associated dementia closely mimics dementia typically seen in the elderly, who are decades older than the individuals most commonly infected with HIV. What makes the brains of these young people act old before their time? The answer may lie in a small protein called a growth factor.

The cells of the body, brain cells included, are in a constantly shifting balance. Old and damaged cells undergo a form of programmed cell death known as apoptosis. While it sounds ominous, apoptosis is necessary to maintain the balance between new cell growth and cell death. Shifting the balance toward uncontrolled cell growth can result in cancer. However, when the balance shifts the other way and too many cells are destroyed, diseases can also arise. In the brain, this excess destruction of cells can lead to dementia.

Researchers at Georgetown University Medical Center discovered that HIV does not directly infect nerve cells, but instead blocks the formation of a growth factor known as mature BDNF (brain derived neurotrophic factor). When the level of this protein decreases in the brain, brain cells are unable to create the long dendritic and axonal branches required to communicate with each other, and die.

The researchers also uncovered the underlying mechanism for this premature cell death. Brain cells release a precursor to the BDNF growth factor called proBDNF. This must be divided by enzymes in the brain to release the active BDNF form, which nourishes brain cells and maintains the connections between them. HIV blocks this division, resulting in high circulating levels of proBDNF. proBDNF binds to a receptor on brain cells that contains a ‘death domain’, triggering apoptosis (cell death).

This HIV-induced imbalance between toxic proBDNF and the healthy form of mature BDNF is similar to the imbalance seen in the aging brain. In a news release from Georgetown University, lead investigator Italo Mocchetti stated ‘“We believe we have discovered a general mechanism of neuronal decline that even explains what happens in some elderly folks. The HIV-infected patients who develop this syndrome are usually quite young, but their brains act old.” Lack of mature BDNF may also play a role in other chronic neurological conditions, including Parkinson’s and Huntington’s Diseases.

The hope is that this new research may eventually lead to the development of drugs effective in multiple forms of dementia. Blocking the receptor for proBDNF could stop the deadly cascade leading to premature cell death, and slow the relentless pace of dementia in both patients with HIV and the elderly.

References

Bachis A, Avdoshina V, Zecca L, Parsadanian M, & Mocchetti I (2012). Human immunodeficiency virus type 1 alters brain-derived neurotrophic factor processing in neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience, 32 (28), 9477-84 PMID: 22787033

Hogan C, & Wilkins E (2011). Neurological complications in HIV. Clinical medicine (London, England), 11 (6), 571-5 PMID: 22268312

Nosheny RL, Mocchetti I, & Bachis A (2005). Brain-derived neurotrophic factor as a prototype neuroprotective factor against HIV-1-associated neuronal degeneration. Neurotoxicity research, 8 (1-2), 187-98 PMID: 16260395

Wendelken LA, & Valcour V (2012). Impact of HIV and aging on neuropsychological function. Journal of neurovirology, 18 (4), 256-63 PMID: 22528478

Image via Sebastian Kaulitzki / Shutterstock.

Margaret McKernan, MD, PhD

Margaret McKernan, MD, PhD, is a practicing diagnostic radiologist and medical writer. She holds an MD/PhD degree in neuroscience from the University of Texas Medical Branch, and completed her graduate medical training in radiology at Wake Forest University Baptist Medical Center and Massachusetts General Hospital.

7 Responses

Terry Michael says:

September 8, 2012 at 11:28 am

Not once in this article does Dr. McKernan acknowledged even the possibility that the highly toxic “anti-retroviral treatments” might be causing the neurological effects she describes from the “research.” Pump enough DNA chain-terminating chemicals into the human body, and you are bound to produce some neurological damage. For evidence of this, read New York magazine’s excellent piece from November 2009:
http://nymag.com/health/features/61740/
..and be sure to watch the embedded video of neurological victims of “HAART.” –Terry Michael
terrymichael@wcpj.org (professional) or terrymichael@terrymichael.net (personal
And, you might want to read the journalism I have written, as a 65-year-old gay man, about the mysterious “HIV” and amorphous “AIDS.”
http://www.terrymichael.net/Htm_InteriorPages/HIV_AIDS_Special_Report.html

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- Ken Howard, LCSW says:
  
  September 17, 2012 at 10:13 pm
  
  More bullshit from an AIDS denialist. You confuse people and undermine their life-saving treatment. My best friend died because of AIDS denialists like you. Fuck you, Sir.
  
  Reply
David Crowe says:

September 9, 2012 at 7:34 pm

And for more (scientific) information on the damage AIDS drugs (ARVs, HAART) can do to the brain and neurological system, please see:
http://aras.ab.ca/haart-nerves.html

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derick karpoff says:

September 12, 2012 at 12:19 am

According to Dr. Margaret McKernan, I am sure dementia patient is more lucky than an HIV patient, while dementia is a severe disease, there are many doctors who have experience with this disease to deal with the old cells symptom. The one with out of luck is an HIV patient, they have to deal with cell destruction, which us incurable by any doctors.

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Ken Howard, LCSW says:

September 17, 2012 at 10:09 pm

I resent the implication of the wording of the last lines of this article: “Blocking the receptor for proBDNF could stop the deadly cascade leading to premature cell death, and slow the relentless pace of dementia in both patients with HIV and the elderly.”

“Relentless pace of dementia”?? Sorry, but that’s an exaggeration. This type of grandiose statement does nothing but promote stigma of HIV, and implies that all people living with HIV are these “demented” crazed dangerous diseased pariahs that should be locked up.

This complication is a risk, and it’s not even that well-quantified. None of the clinical implications (read: real-life impairment) are even described. Clearly, this was written by an HIV-negative person who doesn’t REALLY have contact with HIV-positive people beyond “test subjects”.

I have been living with HIV for 22 years. I’m a licensed psychotherapist who specializes in gay men and HIV, and I’m psychiatric social worker, as well as a professor of graduate clinical social work studies. If there were a “relentless” pace of such dementia, I wouldn’t be able to do what I do for 20 years and counting. Let’s stick with the real issues, shall we, and dispense with the melodramatic, stigmatizing exaggerations.

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