{"id":8458,"date":"2017-07-03T11:03:20","date_gmt":"2017-07-03T11:03:20","guid":{"rendered":"http:\/\/www.neurodegenerationresearch.eu\/?p=8458\/"},"modified":"2017-07-05T08:54:19","modified_gmt":"2017-07-05T08:54:19","slug":"low-levels-of-memory-protein-linked-to-cognitive-decline-in-alzheimers-disease","status":"publish","type":"post","link":"https:\/\/neurodegenerationresearch.eu\/da\/2017\/07\/low-levels-of-memory-protein-linked-to-cognitive-decline-in-alzheimers-disease\/","title":{"rendered":"Low levels of ‘memory protein’ linked to cognitive decline in Alzheimer’s disease"},"content":{"rendered":"

Working with human brain tissue samples and genetically engineered mice, researchers report that consequences of low levels of the protein NPTX2 in the brains of people with Alzheimer\u2019s disease (AD) may change the pattern of neural activity in ways that lead to the learning and memory loss that are hallmarks of the disease.<\/p>\n

This discovery, published in the journal eLife<\/em>, may one day help experts develop new and better therapies for Alzheimer’s and other forms of cognitive decline.<\/p>\n

Clumps of proteins called amyloid plaques, long seen in the brains of people with AD, are often blamed for the mental decline associated with the disease. But autopsies and brain imaging studies reveal that people can have high levels of amyloid without displaying symptoms of AD, calling into question a direct link between amyloid and dementia.<\/p>\n

This new study shows that when the protein NPTX2 is “turned down” at the same time that amyloid is accumulating in the brain, circuit adaptations that are essential for neurons to “speak in unison” are disrupted, resulting in a failure of memory.<\/p>\n

“Immediate early genes\u201d are a set of genes that are activated almost instantly in brain cells when people and other animals have an experience that results in a new memory. The gene NPTX2 is one of these immediate early genes that gets activated and makes a protein that neurons use to strengthen “circuits” in the brain.<\/p>\n

Intrigued by previous studies indicating altered patterns of activity in brains of individuals with Alzheimer\u2019s, the researchers wondered whether altered activity was linked to changes in immediate early gene function.<\/p>\n

To get answers, they first turned to a library of 144 archived human brain tissue samples to measure levels of the protein encoded by the NPTX2 gene. NPTX2 protein levels, they discovered, were reduced by as much as 90 percent in brain samples from people with AD compared with age-matched brain samples without AD. By contrast, people with amyloid plaques who had never shown signs of AD had normal levels of NPTX2. This was an initial suggestion of a link between NPTX2 and cognition.<\/p>\n

To study how lower-than-normal levels of NPTX2 might be related to the cognitive dysfunction of AD, the researchers examined mice bred without the rodent equivalent of the NPTX2 gene.<\/p>\n

Tests showed that a lack of NPTX2 alone wasn’t enough to affect cell function as tested in brain slices. But then the researchers added to mice a gene that increases amyloid generation in their brain. In brain slices from mice with both amyloid and no NPTX2, fast-spiking interneurons could not control brain “rhythms” important for making new memories. Moreover, a glutamate receptor that is normally expressed in interneurons and essential for interneuron function was down-regulated as a consequence of amyloid and NPTX2 deletion in mouse and similarly reduced in human AD brain.<\/p>\n

The researchers say the results suggest that the increased activity seen in the brains of AD patients is due to low NPTX2, combined with amyloid plaques, with consequent disruption of interneuron function. And if the effect of NPTX2 and amyloid is synergistic — one depending on the other for the effect — it would explain why not all people with high levels of brain amyloid show signs of AD.<\/p>\n

The scientists then examined NPTX2 protein in the cerebrospinal fluid (CSF) of 60 living AD patients and 72 people without AD. Lower scores of memory and cognition on standard AD tests, they found, were associated with lower levels of NPTX2 in the CSF. Moreover, NPTX2 correlated with measures of the size of the hippocampus, a brain region essential for memory that shrinks in AD. In this patient population, NPTX2 levels were more closely correlated with cognitive performance than current best biomarkers — including tau, a biomarker of neurodegenerative diseases, and a biomarker known as A-beta-42, which has long been associated with AD. Overall, NPTX2 levels in the CSF of AD patients were 36 to 70 percent lower than in people without AD.<\/p>\n

According to the researchers, NPTX2 could constitute a new mechanism that has not previously been studied in animal models, and for this reason could lead to exciting new discoveries. More work is needed, they say, to understand why NPTX2 levels become low in AD and how that process could be prevented or slowed.<\/p>\n

Paper: \u201cNPTX2 and cognitive dysfunction in Alzheimer\u2019s Disease\u201d<\/a><\/a><\/strong>
\nReprinted from materials provided by\u00a0Johns Hopkins Medicine<\/a>.<\/strong><\/p>\n","protected":false},"excerpt":{"rendered":"

Working with human brain tissue samples and genetically engineered mice, […]<\/p>\nView Post<\/a>","protected":false},"author":3,"featured_media":3351,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[22],"tags":[],"class_list":["post-8458","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-research-news"],"acf":[],"yoast_head":"\nLow levels of 'memory protein' linked to cognitive decline in Alzheimer's disease - JPND Neurodegenerative Disease Research<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/neurodegenerationresearch.eu\/2017\/07\/low-levels-of-memory-protein-linked-to-cognitive-decline-in-alzheimers-disease\/\" \/>\n<meta property=\"og:locale\" content=\"da_DK\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Low levels of 'memory protein' linked to cognitive decline in Alzheimer's disease - 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