Astrocytes implicated in preclinical AD

Feb 12 2016

By Eleanor McDermid, Senior medwireNews Reporter

Astrocytes are activated in the brains of people with autosomal dominant Alzheimer’s disease (AD) long before symptoms appear and even before amyloidosis begins, a study shows.

Researchers compared positron emission tomography findings from 27 members of families with autosomal dominant AD; seven of these were mutation carriers with no symptoms, four had mutations and were symptomatic and 16 were noncarriers.

Based on the binding of the tracer ¹¹C-DED to the astrocyte activation marker monoamine oxidase-B (MAOB), Agneta Nordberg (Karolinska Institutet, Stockholm, Sweden) and team calculated that astrocyte activation is markedly increased in mutation carriers versus noncarriers around 25 years before the expected onset of symptoms.

This preceded amyloid deposition, which they estimate begins from around 17 years before symptom onset, with the earliest appearance being in the putamen.

The early activation of astrocytes could be caused by high levels of soluble β-amyloid, the team suggests in Brain.

But this initial high activation of astrocytes declined steeply over subsequent years, falling to the levels seen in noncarriers prior to the estimated date of symptom onset. The steepest falls were in the caudate nucleus and the thalamus.

“Decreasing MAOB expression in astrocytes with the progression of the disease may be an indication of a reduction in a certain type of astrocyte activation or functionality, a change of astrocyte activation phenotype, or possibly ‘astrodegeneration’ and astrocyte cell loss itself, as has been reported towards the late stages of Alzheimer’s disease”, say Nordberg et al.

The team also assessed 25 patients with sporadic AD, including four with mild cognitive impairment (MCI) and no evidence of amyloid deposition, 13 with MCI and amyloid deposition and eight with overt AD. Astrocyte activation was detectable in these groups, but was less elevated than in presymptomatic autosomal dominant AD and did not significantly change over the disease course.

The researchers suggest this could be because the sporadic AD patients were not detected as early in the disease course as the AD mutation carriers were, or because astrocytosis follows different courses in the familial and sporadic forms of AD.

“Future research on earlier stages in at-risk sporadic cohorts would help elucidate whether sporadic Alzheimer’s disease has a similar regional pattern of early brain astrocytosis to that observed in [autosomal dominant] AD”, they conclude.

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