New clues to Alzheimer’s disease

first_imgResearchers probing the complexities of Alzheimer’s disease have detected issues involving cellular energy production, and those problems may be an important contributor to the late-onset form of the illness.A team at Harvard-affiliated McLean Hospital tested the cells of late-onset Alzheimer’s patients and found malfunctions in their energy production, including problems with the health of their mitochondria, the cellular power plants that provide most of their energy.Bruce Cohen, director of McLean’s Program for Neuropsychiatric Research and the Robertson-Steele Professor of Psychiatry at Harvard Medical School (HMS), said disrupted energy production would present particularly severe problems in the brain, because it is the body’s most energy-hungry organ, demanding as much as 20 times the energy of other tissues. Such a malfunction, he said, could damage or kill nerve cells and help explain the cognitive decline associated with the disease.Much of the scientific attention focused on Alzheimer’s has centered on what’s called the amyloid cascade hypothesis. That suggests that a protein called amyloid-beta forms plaques in the brain, triggering tangles made up of a second protein called tau, which sets off the inflammation that destroys neurons and leads to Alzheimer’s signature cognitive decline.The problem with that hypothesis, according to Kai Sonntag, associate stem cell researcher at McLean and assistant professor of psychiatry at HMS, is that it’s not uncommon to examine the brains of cognitively normal older people after they’ve died and find similar plaques and tangles. In addition, Alzheimer’s drugs developed to target amyloid-beta have failed to halt or reverse cognitive decline. That indicates that something else — or something in addition — is likely in play, Sonntag and Cohen said,“I do think there’s a need in the field to look at different angles,” Sonntag said.Lending additional complexity to the Alzheimer’s picture are differences between its two forms: early onset — which, though relatively rare, has been intensively studied — and late-onset, which accounts for 95 percent of the cases. Early onset Alzheimer’s is a particularly severe form that runs in families whose members develop the disease in their 50s and early 60s. It has been traced to a handful of genetic mutations that produce heavy loads of amyloid plaques in the brain. Insights from early onset Alzheimer’s have informed medical understanding of the disease more broadly, while the identified genetic mutations have been used to create mouse models of the ailment so it can be better studied in the lab, Sonntag said.But it’s possible that lessons from those studies may not neatly apply to the late-onset form, called sporadic Alzheimer’s, which typically strikes after age 65, Sonntag said. While the two forms of Alzheimer’s share many features — including heightened risk if there is a history of Alzheimer’s in the family, the development of plaques and tangles in the brain, and the hallmark cognitive decline — Sonntag and Cohen said late-onset Alzheimer’s could be an aberration of the normal aging process.“You could say maybe sporadic disease isn’t like early onset disease, but a reflection of abnormal aging,” Sonntag said. “Every aspect of Alzheimer’s disease you can [also] find in normal aging. Accumulation of [amyloid]-beta occurs in all of us, phosphorylation of tau, all these things. Even when you look at post-mortem brains, there’s a high percentage of people with high levels of [amyloid]-beta, but who are not demented. There’s no 100 percent correlation between accumulation of plaque and Alzheimer’s disease, even when you look at post-mortem brains.”The work grew out of Cohen’s prior research, which looked at the role of cellular energy dysfunction in psychiatric diseases. With aging also marked by reduced cellular energy production and Alzheimer’s, particularly the late-onset form, tied to aging, it was a short leap to wonder whether dysfunctions similar to those seen in psychiatric disorders might contribute to Alzheimer’s, Cohen said.“Energy production and use seem to be one thing that goes wrong [in cells] as we get older,” Cohen said. “We do see changes with aging, and we do see changes that are shared with aging and Alzheimer’s, but also some changes that are specific to Alzheimer’s.”In work published recently in the journal Scientific Reports, Cohen, Sonntag, and colleagues at McLean took a type of skin cells called fibroblasts from late-onset Alzheimer’s patients and compared their energy production with those of age-matched controls without Alzheimer’s. Because energy metabolism is largely genetically determined, it’s likely that what was occurring in the fibroblasts was replicated throughout the body, including the neurons.Cells typically produce most of their energy (88 percent) through mitochondrial respiration, which takes place inside a cell’s mitochondria. A smaller amount (12 percent) is produced through a process called glycolysis. The researchers showed that skin cells from late-onset Alzheimer’s patients had impaired mitochondrial metabolic potential and shifted their energy production toward glycolysis to compensate.The brain, however, is not only energy-hungry, its neurons are handicapped compared with fibroblasts, according to Sonntag. That’s because neurons make energy primarily through mitochondrial respiration, and so don’t have the process of glycolysis to fall back on. That means impaired mitochondrial respiration could result in the death of neurons, which could help explain Alzheimer’s cognitive decline.If energy dysfunction is shown to play a role, Cohen said, it’s likely just a piece of the Alzheimer’s puzzle, one affected by multiple factors interacting in complex ways to provide outcomes that differ in various patients.“Although people hope with a lot of these conditions we study — normal or abnormal — that there are going to be simple answers … it’s never simple, it’s always all kinds of factors interacting to determine whether you get lucky or not, whether you get sick or not,” Cohen said.The next step, Cohen said, will be to do a similar study on the neurons and other brain cells of Alzheimer’s patients, to see whether the energy dysfunction detected in skin cells is replicated there. Even if medical understanding of the disease remains imperfect, Cohen said the ultimate hope is to find an intervention that interrupts Alzheimer’s most devastating effects.“You don’t have to fix everything to keep somebody from getting sick,” Cohen said. “The reason somebody gets sick is you’re unlucky five different ways and it all combines to tip you over the edge. Maybe you only need to fix one of them and you don’t tip over the edge anymore.”last_img read more

Local Excise Officer Loses Long Fight To Cancer

first_imgLeslie Noble Stratton (Image: Indiana State Excise)HOLTON – Family, friends and colleagues are mourning the loss of a local excise officer who passed away Wednesday morning after a long and courageous battle with cancer.Sgt. Leslie Noble Stratton, of Holton, graduated from Jac-Cen-Del High School in 1973, when he joined the United States Army. He served in the military for three years and was promoted to Sergeant.Stratton joined the Indiana State Excise Police on Jan.  8, 1979, after completing an internship with the agency as a student at Vincennes University, from which he earned his associates degree.He was initially assigned to the Vincennes district before transferring to the Seymour Area where he served the remainder of his career. He was promoted to Sergeant in 1987 and received the departments Educator of the Year award in 1997.“It is with heavy hearts that we bid farewell to our friend and colleague, Les,” Superintendent Matt Strittmatter said. “During my time as superintendent, I found Les to be a man of few words; however, when he spoke, he offered much wisdom.  This is the result of his experience as an excise officer and his dedication to doing his part to ensure the safety of Indiana citizens.  He will be greatly missed by the department, and our heartfelt condolences and prayers go out to his family.”Sgt. Stratton is survived by his wife, Vernice (Owens) Stratton, of Holton, Ind.; his son, Roger Stratton and his wife, Rhonda Stratton, of Holton, Ind.; his daughter, Jennifer Nicholson, and her husband, Hank Nicholson, of Versailles, Ind.; and his daughter-in-law, Katherine Hiatt. He was preceded in death by his son, Scott Stratton, in 2003.Sgt. Stratton is also survived by six grandchildren: Emmett Stratton, Levi Stratton, Emma Hiatt, Lanie Nicholson, Lucie Nicholson and Clint Nicholson.Funeral arrangements are pending.last_img read more

Trojans Grapplers Capture Sectional Crown-Lots Of Area Regional Qualifiers

first_imgThe East Central Trojans Wrestling team continue their winning ways this season by capturing The Wrestling Sectional Team Championship at Franklin on Saturday, February 1st, at Franklin County. Coach Adam Wolf’s squad won six individual weight titles en route to repeating as Sectional Champs and all Trojans Wrestlers participating also Regional bound. The overall team results. 2-Milan, 3-South Dearborn, 4-Rushville, 5-Lawrenceburg, 6-Franklin County, 7-Connersville, 8-Greensburg, 9-Batesville, 10-Union County.The Batesville High School wrestling team traveled to Franklin County to compete in Sections with 9 other teams. Despite the 9th place finish, The Bulldogs had a strong individual performance with half the team that participated in placing and 3 moving on to regionals.Sophomore Josh Mobley had the best finish with a 2nd place finish at 152. Mobley went 2-1 with a pin and a 9-3 victory. Josh lost in the finals to number 3 ranked Bryar Hall form East Central. JT Linkel went 3-1 on his way to a 3rd place finish at 145. Linkel had 1 pin and 2 decision victories. Alex Murphy went 2-2 finishing 4th with 2 pins. All three will be moving on to regionals next week in Richmond. Seniors Nick Nobbe and Axel Garcia both placed 6th at 160 and 170. Other participants were Jonathan Lamping at 126, Jonathan Schrank at 138, Jy’lil Chappell at 182, Christian Garcia at 195, and Brandon Manning at 220. The team placed 9th with 55 points.Failed to fetch Error: URL to the PDF file must be on exactly the same domain as the current web page. Click here for more infoFailed to fetch Error: URL to the PDF file must be on exactly the same domain as the current web page. Click here for more infoThe top four wrestlers from each individual weight class will advance to The Regionals at Richmond on Saturday, February 8th, starting at 9 AM.Congrats to our area qualifying wrestlers at The Sectionals and good luck at The Regionals.last_img read more

Ministry reads riot act to NFA, Clubs over resumption of league

first_imgRelatedPosts Minister gives condition for resumption of contact sports Minister pledges support for development of AI, robotics in Nigeria NSF 2020: Sports minister raises fresh hope The Minister of Youth and Sports Development, Sunday Dare, has read out the riot acts to the Nigerian Football Federation and club owners that no stadium would be opened for any football game without strict adherence to the sports protocols, even as there must be total  implementation of the club licensing control before the new football season can resume.This was contained in a statement by the Permanent Secretary of the Ministry, Gabriel Aduda, on Sunday. Aduda said: “We are happy that the ban on sports has been lifted after so many months of inactivity due to the COVID-19 scourge. The Ministry is not oblivious of the challenges that would be encountered in organising football matches.“We cannot take anything for granted. As a way of safeguarding  the lives of our players, coaches, officials  and fans, approval must be sought and given before any game is played. The Ministry would ensure that all protocols and guidelines are obeyed as directed by PTF and NCDC.”The Ministry has set up a COVID-19 monitoring and approval team, which would ensure compliance before any game is played.Aduda warned that the Nigerian domestic league would not resume until basic conditions are fulfilled.He said: “We have a responsibility to enforce the implementation of the club licensing control as stipulated in the statues setting up the Nigerian Professional Football League. The domestic League will not commence until the regulations and controls bothering on financial and licensing control are enforced. “The NFF must enforce these regulations and controls  as stipulated, otherwise the Nigerian Professional and  Amateur Leagues would not be approved to  resume. These include proper licensing of players, Insurance for players and coaches, compliance with FIFA rules on players contract and transfer, running  the clubs as professional endeavour  among others.”The statement directed the NFF to communicate these decisions to the clubs to forestall any crisis.Tags: Gabriel AdudaNFANFFSunday Darelast_img read more

Kerry and Mayo draw in Croke Park thriller

first_imgThey added a further three points from the boot of Johnny Buckley midway through the second half.The Munster champions led by a point entering the 74th minute of the game before a Paddy Durcan equaliser ensured the two sides must do it again.The replay has been scheduled for 3pm on Saturday at the same venue.Mayo arguably came through a tougher run-in to the game, seeing off Derry and Cork after extra-time in the qualifiers while taking two attempts to beat Roscommon.Kerry enjoyed a more comfortable passage to the last four, but manager Eamonn Fitzmaurice says he doesn’t think that contributed to their slow start. Croke Park will play host to next Saturday’s All-Ireland football semi-final replay after Kerry and Mayo played out a thriller yesterday.Despite awful conditions at headquarters, both sides were able to live up to the pre-match hype for a game which included four goals.Three of those came in the opening 20 minutes, with Andy Moran and Colm Boyle finding the back of the net for Mayo, and Stephen O’Brien getting the goal for the Kingdom.last_img read more