Chemical changes in hippocampus are early diagnostic clues for Alzheimer disease | KurzweilAI


Various brain disorders and associated alterations of pH in different brain regions. The pH is increased in epilepsy (region: temporal lobes), in panic disorder (region: frontal lobes), and in Alzheimer’s disease (region: hippocampus area) and decreased in bipolar disorder (region: frontal lobes). There is no change in pH in Parkinson’s disease patients (during visual-stimulation), white matter damage, schizophrenia, sleep deprivation, or hypoxic hypoxia cases.(Credit: Pravat K. Mandal, et al./Journal of Alzheimer’s Disease)

Dr. Pravat K. Mandal and colleagues have developed a non-invasive brain imaging technique that measures specific brain chemical changes in the hippocampus, providing a signature of the early stages of Alzheimer disease.

Key findings in pre-Alzheimer and Alzheimer disease patients in the left hippocampus:

  • Increase in pH to the alkaline range.
  • Changes in four brain chemicals.

This diagnostic technique requires no blood work or radiation, and can be conducted in less than fifteen minutes, says Dr. Mandal, who is associated with the National Brain Research Center, Gurgaon, India, and Johns Hopkins University School of Medicine. “It may offer hope to Alzheimer’s disease patients and their families.”

Hippocampus chemistry changes

Dr. Mandal and his co-investigators studied the brains of normal controls, AD patients, and patients with mild cognitive impairment (MCI). They used multi-voxel 31P magnetic resonance spectroscopy (MRS) imaging, using an MRI machine, along with an advanced analytical tool, to assess brain chemistry in the hippocampal regions.

Spectrum obtained from the left and the right hippocampus regions in control subjects (credit: Pravat K. Mandal, et al./Journal of Alzheimer’s Disease)

Spectrum obtained from the left and the right hippocampus regions in AD subjects (credit: Pravat K. Mandal, et al./Journal of Alzheimer’s Disease)

They found that the left hippocampus becomes alkaline in AD patients, which is in contrast to the normal aging process, in which the brain tends to be more acidic.

Dr. Mandal and his colleagues also identified four brain chemicals that change significantly in pre-Alzheimer and Alzheimer disease patients compared to normal subjects: phosphomonoester (PME), the building block of neuronal membrane; phosphodiester (PDE), the membrane degradation product; phosphocreatine (PCr), stored energy for brain functioning; and adenosine triphosphate (-ATP), the source of brain energy.

The level of PME is significantly decreased in the left hippocampal areas of these patients, and the levels of PDE, PCr, and -ATP are increased. Also in the left hippocampus, there is an increase in pH to the alkaline range, along with statistically significant increases in PDE, PCr, and -ATP and decreases in PDE, notes Dr. Mandal.

The researchers plan to conduct longitudinal studies with Alzheimer and Parkinson patients with larger sample sizes to investigate specificity of their test. “It is our hope that such clinical research, using state-of-the-art technology, may give new hope to cognitively impaired patients for an earlier and more predictable AD diagnosis,” said Dr. Mandal.

Alzheimer’s disease (AD) is a major neurodegenerative disorder that affects millions of people worldwide. New and accurate techniques for early diagnosis are critical.

Ref.: Pravat K. Mandal, et al., Mapping of Hippocampal pH and Neurochemicals from in vivo Multi-Voxel 31P Experiments in Healthy Normal Young Male/Female, Mild Cognitive Impairment, and Alzheimer’s Disease, Journal of Alzheimer’s Disease, 2012, DOI: 10.3233/JAD-2012-120166


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