Summary: Researchers report a on a correlation between higher levels of NPTX2 and better brain volume and memory.
Source: Iowa State University.
Iowa State University researchers have identified a protein essential for building memories that appears to predict the progression of memory loss and brain atrophy in Alzheimer’s patients.
Auriel Willette, an assistant professor of food science and human nutrition; and Ashley Swanson, a graduate research assistant, say the findings also suggest there is a link between brain activity and the presence of the protein neuronal pentraxin-2, or NPTX2. The research, published in the journal Brain, Behavior and Immunity, found a correlation between higher levels of NPTX2 and better memory and more brain volume. Lower levels of the protein were associated with diminished memory and less volume.
“NPTX2 seems to exert a protective effect,” Swanson said. “The more you have, the less brain atrophy and better memory you have over time.”
The discovery is encouraging as it offers an avenue to track the progression of Alzheimer’s disease over time, but it also generates a lot of questions. Researchers want to know how best to boost NPTX2 levels and if there is an added benefit. They were struck by a trend in the data that points to a possible answer. Study participants with more years of education showed higher levels of the protein. Willette says people with complex jobs or who stay mentally and socially active could see similar benefits, supporting the notion of “use it or lose it.”
“You’re keeping the machinery going,” Willette said. “It makes sense that the more time spent intensely focused on learning, the more your brain is trained to process information and that doesn’t go away. That intense kind of learning seems to make your brain stronger.”
Good vs. bad proteins
Willette and Swanson used data from the Alzheimer’s Disease Neuroimaging Initiative to assess which aspects of the immune system were most relevant to tracking Alzheimer’s disease progression. They consistently found two proteins (NPTX2 and Chitinase-3-like-protein-1, or C3LP1) that predicted aspects of the disease. Among 285 older adults, they examined memory performance at baseline, six months, one year and two years. At the beginning of the study, 86 participants had normal brain function, 135 expressed mild cognitive impairment (the precursor to Alzheimer’s), and 64 had Alzheimer’s disease.
ISU researchers also focused their attention on the medial temporal lobe, an area of the brain that shows the first signs of memory loss or cognitive decline in Alzheimer’s disease. While C3LP1 modestly predicted atrophy in the medial temporal lobe, it did not track memory decline over time, researchers said. After two years, the presence of NPTX2 explained 56 percent of the fluctuation in memory loss and 29 percent of medial temporal lobe volume.
Willette and Swanson say they were somewhat surprised by the comparative results. They expected C3LP1, which causes brain inflammation and is thought to degrade the brain and memory, to be a stronger indicator. However, the memory forming benefits of NPTX2 proved to be consistently significant during the two years that researchers tracked memory decline and medial temporal lobe atrophy.
“We see this as a promising biomarker that affects a lot of key aspects of Alzheimer’s disease,” Swanson said. “It’s a revolutionary approach and we’re looking at it in a more holistic way, rather than a reductionist viewpoint, to understand how the immune system and brain are connected.”
Willette added, “With this disease you have to be comprehensive. There are so many aspects of our environment, our lifestyle, our immune system that influence the degree to which you’re at risk for Alzheimer’s disease.”
Source: Auriel Willette – Iowa State University Image Source: This NeuroscienceNews.com image is credited to DBCLS and is licensed CC BY SA 2.1 jp. Original Research: Full open access research for “Neuronal Pentraxin 2 predicts medial temporal atrophy and memory decline across the Alzheimer’s disease spectrum” by Ashley Swanson, A.A. Willette, for the Alzheimer’s Disease Neuroimaging Initiative in Brain, Behavior and Immunity. Published online July 18 2016 doi:10.1016/j.bbi.2016.07.148
Cite This NeuroscienceNews.com Article
[cbtabs][cbtab title=”MLA”]Iowa State University. “”Use it or Lose it” to Defend Against Memory Loss.” NeuroscienceNews. NeuroscienceNews, 4 August 2016. <https://neurosciencenews.com/memory-loss-neuroscience-atrophy-4777/>.[/cbtab][cbtab title=”APA”]Iowa State University. (2016, August 4). “Use it or Lose it” to Defend Against Memory Loss. NeuroscienceNews. Retrieved August 4, 2016 from https://neurosciencenews.com/memory-loss-neuroscience-atrophy-4777/[/cbtab][cbtab title=”Chicago”]Iowa State University. “”Use it or Lose it” to Defend Against Memory Loss.” https://neurosciencenews.com/memory-loss-neuroscience-atrophy-4777/ (accessed August 4, 2016).[/cbtab][/cbtabs]
Neuronal Pentraxin 2 predicts medial temporal atrophy and memory decline across the Alzheimer’s disease spectrum
Chronic neuroinflammation is thought to potentiate medial temporal lobe (MTL) atrophy and memory decline in Alzheimer’s disease (AD). It has become increasingly important to find novel immunological biomarkers of neuroinflammation or other processes that can track AD development and progression. Our study explored which pro- or anti-inflammatory cerebrospinal fluid (CSF) biomarkers best predicted AD neuropathology over 24 months. Using Alzheimer’s Disease Neuroimaging Initiative data (N = 285), CSF inflammatory biomarkers from mass spectrometry and multiplex panels were screened using stepwise regression, followed up with 50%/50% model retests for validation. Neuronal Pentraxin 2 (NPTX2) and Chitinase-3-like-protein-1 (C3LP1), biomarkers of glutamatergic synaptic plasticity and microglial activation respectively, were the only consistently significant biomarkers selected. Once these biomarkers were selected, linear mixed models were used to analyze their baseline and longitudinal associations with bilateral MTL volume, memory decline, global cognition, and established AD biomarkers including CSF amyloid and tau. Higher baseline NPTX2 levels corresponded to less MTL atrophy [R2 = 0.287, p < 0.001] and substantially less memory decline [R2 = 0.560, p < 0.001] by month 24. Conversely, higher C3LP1 modestly predicted more MTL atrophy [R2 = 0.083, p < 0.001], yet did not significantly track memory decline over time. In conclusion, NPTX2 is a novel pro-inflammatory cytokine that predicts AD-related outcomes better than any immunological biomarker to date, substantially accounting for brain atrophy and especially memory decline. C3LP1 as the microglial biomarker, by contrast, performed modestly and did not predict longitudinal memory decline. This research may advance the current understanding of AD etiopathogenesis, while expanding early diagnostic techniques through the use of novel pro-inflammatory biomarkers, such as NPTX2. Future studies should also see if NPTX2 causally affects MTL morphometry and memory performance.
“Neuronal Pentraxin 2 predicts medial temporal atrophy and memory decline across the Alzheimer’s disease spectrum” by Ashley Swanson, A.A. Willette, for the Alzheimer’s Disease Neuroimaging Initiative in Brain, Behavior and Immunity. Published online July 18 2016 doi:10.1016/j.bbi.2016.07.148