MR may detect earliest Alzheimer's brain changes

By Eleanor McDermid

Levels of the brain metabolite and neuroinflammation marker myo-inositol are elevated in asymptomatic patients with abnormal Alzheimer's disease (AD) biomarkers, say researchers.

As reported in Neurology, people who were cognitively normal but had reduced levels of β-amyloid (Aβ) in the cerebrospinal fluid had significantly increased ratios of myo-inositol to creatinine and N-acetylaspartate, relative to controls with normal Aβ levels.

"Insofar as [myo-inositol] reflects neuroinflammation, its measurement may have a role in monitoring disease progression", write Kejal Kantarci (Mayo Clinic, Rochester, Minnesota, USA) and Terry Goldberg (Hofstra Northwell School of Medicine, Hempstead, New York, USA) in an accompanying editorial.

The researchers used proton magnetic resonance (MR) spectroscopy data from 352 participants of the prospective Swedish BioFINDER cohort study.

"MR markers of AD-related pathophysiology have the advantage in accessibility and cost, and lack of radioactive injections", observe the editorialists.

Besides being elevated in the cognitively normal group with low Aβ levels, the ratio of myo-inositol to creatinine rose with decreasing Aβ across the whole cohort, which included people with low Aβ and normal cognition (n=59), subjective cognitive problems (n=49) or mild cognitive impairment (n=88).

The cohort also included 156 people who had both normal cognition and normal AD biomarkers. Within this group, Olga Voevodskaya (Karolinska Institute, Stockholm, Sweden) and co-researchers found that carriers of the APOE ε4 allele had a significantly higher average myo-inositol/creatinine ratio than noncarriers.

They suggest therefore that measuring the myo-inositol/creatinine ratio "has the potential to detect manifestations of the APOE genetic effect, which precede cognitive decline and may antedate or be independent of amyloid pathology, perhaps even detecting the more pronounced proinflammatory state associated with ε4 carriership."

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