• Alzheimer's

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"Suspected Non-Alzheimer Pathophysiology" or SNAP, a puzzling set of symptoms that might or might not indicate Alzheimer's disease, probably isn't going to progress to Alzheimer's, according to two new studies.

SNAP describes cognitively normal older adults with one of several markers of neurodegeneration but test negative for brain amyloid and have not been diagnosed with a specific neurodegenerative disorder. It's clear SNAP isn't a preclinical stage of Alzheimer's but scientists can't decide on what it is exactly.

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One of the studies, this from the Knight Alzheimer Disease Research Center at Washington University in St. Louis, found the same low proportion (14% to 17%) of those with SNAP and those with no pathology at baseline went on to have amyloid accumulation in their brains, said Brian Gordon, PhD and his colleagues.

The other study from the Harvard Aging Brain Study shows people with SNAP didn't have greater levels of tau in Alzheimer's brain regions than those without any pathology, according to Elizabeth Mormino, PhD, and colleagues. Some studies suggest the tau protein might better predict Alzheimer's disease and dementia.

Gordon said there's a disconnect between those with SNAP and those on an Alzheimer's trajectory, according to MedPage Today. He believes something else is going on with the neurodegeneration seen in SNAP.

SNAP was first reported in 2012 by Clifford Jack, MD, David Knopman, MD, of the Mayo Clinic and others. Since then, its remained a puzzle to Alzheimer's researchers.

Patients are said to have SNAP if they have no amyloid buildup in their brains, but have another biomarker of neurodegeneration such as cerebrospinal tau levels or brain volume changes on MRI.

The finding came up when the National Institute on Aging and the Alzheimer's Association developed research criteria for preclinical Alzheimer's disease. The new criteria includes three stages: having amyloid but no neurodegeneration (Stage 1); having amyloid plus neurodegeneration (Stage 2), or having amyloid and neurodegeneration with subtle cognitive changes (Stage 3).

Across studies, about a quarter of patients don't fit into those categories, and instead have evidence of neurodegeneration without any amyloid deposition.

Separate studies to better understand SNAP by Gordon and Mormino found that 14% to 17% of those with SNAP later went on to have amyloid accumulation. This, however, was the same rate at which participants with no amyloid and no neurodegeneration (those in 'Stage 0' of the NIA-AA criteria) went on to develop amyloid accumulation, they reported. Nor was there any difference in loss of hippocampal volume between these two groups.

"This suggests that even though a percentage of SNAP patients show a typical Alzheimer's pattern, it's no different from people who are completely healthy at baseline," said Gordon.

"This argues against SNAP being some sort of accelerated Alzheimer's pathology, and instead it's more likely that this is some other form of neurodegeneration."