Breaking News
January 23, 2019 - Short interval between last meal of the day and bedtime may not affect blood glucose levels
January 23, 2019 - Still Too Many Highway Deaths Tied to Speeding
January 23, 2019 - Prenatal valproate exposure linked to increased ADHD risk
January 23, 2019 - Compound identified that may help treat heart failure
January 23, 2019 - Undiagnosed Asthma in Urban Adolescents May Be Common
January 23, 2019 - Study describes metabolism of intestinal microbiota in babies for the first time
January 22, 2019 - Study links concussions to development of epilepsy
January 22, 2019 - Specialist-led hospital bereavement service may help restrain legal action after difficult deaths
January 22, 2019 - Genetic study reveals possible new routes to treating osteoarthritis
January 22, 2019 - Blood test may detect early signs of lung-transplant rejection
January 22, 2019 - Blood marker could aid in early prediction of Alzheimer’s progression
January 22, 2019 - Orthodontic treatment does not guarantee future dental health
January 22, 2019 - Rutgers researchers discover cause of bone loss in people with joint replacements
January 22, 2019 - Diversity among rural Africans extends to their gut microbiomes
January 22, 2019 - Newly developed biological system lets cells to create self-curving cornea
January 22, 2019 - VTv Therapeutics Announces Publication of Comprehensive Data in Science Translational Medicine Detailing the Discovery and Clinical Development of TTP399, including Results of Phase 2 AGATA Study
January 22, 2019 - about one in three adults with prediabetes has arthritis
January 22, 2019 - A look at how data is democratizing health care
January 22, 2019 - Alcohol-Linked Disease Overtakes Hep C As Top Reason For Liver Transplant
January 22, 2019 - Researchers identify new genes linked with age-related macular degeneration
January 22, 2019 - MPFI researchers identify synaptic logic for connections between two brain hemispheres
January 22, 2019 - New study extends our knowledge of the link between miRNAs and cancer
January 22, 2019 - Asthma, eczema are not barriers to active lifestyle in teenagers
January 22, 2019 - Genetic changes may predict likelihood of relapse in breast cancer patients
January 22, 2019 - Antiepileptic drug use by people with Alzheimer’s disease linked to accumulation of hospital days
January 22, 2019 - IUPUI researcher receives $2.85 million grant to find ways to improve bone strength
January 22, 2019 - Precision medicine can help keep astronauts healthy during deep space missions
January 22, 2019 - Detecting signs of neurodegeneration earlier and more accurately
January 22, 2019 - Mouse studies challenge ‘inhibition’ theory of autism
January 22, 2019 - SSB launches BIOSTAT RM TX single-use bioreactor for producing consistent quality cellular products
January 22, 2019 - Experimental drug can positively modify key characteristic behavior in FXS patients
January 22, 2019 - Low-Income Women Lack Menstrual Hygiene Supplies
January 22, 2019 - Better mouse model built to enable precision-medicine research for Alzheimer’s
January 22, 2019 - Molecular profiling of precancerous lung lesions could lead to early detection and new treatments
January 22, 2019 - Genetic factors influence where fat is stored in our bodies
January 22, 2019 - The Psychology Behind Sticking to Your New Year’s Resolutions
January 22, 2019 - Scientists aim to find genetic causes of developmental abnormalities in the vagina and uterus
January 22, 2019 - New survey reveals scale of preventative healthcare challenge in the UK
January 22, 2019 - Looming Global Crisis Means People’s Diets Must Change: Experts
January 22, 2019 - Excessive social media use is comparable to drug addiction
January 22, 2019 - Researchers show how mechanical stress affects bone development
January 22, 2019 - Study takes a step closer to understanding the body’s response to opioid painkillers
January 22, 2019 - Unexpected connection found between feeding and memory centers of the brain
January 22, 2019 - A revolutionary approach transforms bone trauma treatment
January 22, 2019 - Early studies and recent clinical trials on nerve growth factor
January 22, 2019 - Dry Mouth and Older Adults: Information for Caregivers
January 22, 2019 - Are your grandparents getting tipsy at the holiday party?
January 22, 2019 - New machine learning algorithms identify early symptoms of urinary tract infections
January 22, 2019 - Young women skipping the Pap smear test due to embarrassment
January 22, 2019 - A global influenza pandemic high on the WHO’s agenda
January 22, 2019 - Amgen Makes All Repatha (evolocumab) Device Options Available In The US At A 60 Percent Reduced List Price
January 22, 2019 - Elastronics—hydrogel-based microelectronics for localized low-voltage neuromodulation
January 22, 2019 - Branched-chain amino acids in tumors can be targeted to prevent and treat cancer
January 22, 2019 - Fueling macrophages with energy to attack and eat cancer cells
January 22, 2019 - Amgen And UCB Receive Positive Vote From FDA Advisory Committee In Favor Of Approval For Evenity (romosozumab)
January 22, 2019 - Does being bilingual make children more focused? Study says no
January 22, 2019 - Study reveals new genes and biological pathways linked to osteoarthritis
January 22, 2019 - FSU study provides better understanding of spinal cord injuries
January 22, 2019 - Delaying bath for newborn babies increases breastfeeding rates, finds study
January 21, 2019 - WHO identifies non-communicable diseases as major threat to human health
January 21, 2019 - Many parents still try non-evidence-based cold prevention methods for children
January 21, 2019 - High Levels of Activity, Motor Ability Linked to Better Cognition
January 21, 2019 - Killer blows? Knockout study of pair of mouse MicroRNA provides cancer insight
January 21, 2019 - Buffalo researchers receive grant to quicken development of generic equivalents of contraceptives
January 21, 2019 - One-third of pregnant women do not believe cannabis is harmful to their fetus
January 21, 2019 - Fiderstat could be used as chemopreventative drug for intestinal cancers caused by APC gene mutations
January 21, 2019 - Modifying healthcare delivery practices may improve discussions between youth and healthcare providers
January 21, 2019 - UNIST researcher named as recipient of Merck’s 2018 Life Science Awards
January 21, 2019 - How Getting a Flu Shot Could Save Your Life
January 21, 2019 - Surgical adhesions can be treated, prevented in mice
January 21, 2019 - Increased physician-targeted marketing associated with higher opioid overdose deaths
January 21, 2019 - Researchers uncover specific microbial signatures of intestinal disease
January 21, 2019 - Researchers discover new blood vessel system in bones
January 21, 2019 - Simple blood test reliably detects signs of Alzheimer’s damage before symptoms
January 21, 2019 - Study to investigate new targeted oral treatments for severe asthma
January 21, 2019 - Plan Your Plate | NIH News in Health
January 21, 2019 - Fecal occult blood test may improve CRC outcomes in some
January 21, 2019 - Blood test detects Alzheimer’s disease years before symptoms develop
January 21, 2019 - Mount Sinai joins with Paradigm and ReqMed to repurpose drug for treatment of MPS
January 21, 2019 - FDA Advisory Committee Votes on Zynquista (sotagliflozin) as Treatment for Adults with Type 1 Diabetes
New Alzheimer’s animal model more closely mimics human disease

New Alzheimer’s animal model more closely mimics human disease

image_pdfDownload PDFimage_print
Upper panel: Tau clumps in new AD mouse model, either in the cell body as neurofibrillary tangles (NFTs) or in dystrophic axons surrounding A-beta plaques as neuritic plaque tau. Lower panel: tau clumps in human AD brain, as NFTs (arrow head) and NP tau. Credit: The lab of Virginia Lee, PhD, Perelman School of Medicine, University of Pennsylvania

By injecting human Alzheimer’s disease brain extracts of pathological tau protein (from postmortem donated tissue) into mice with different amounts of amyloid-β (Aβ) plaques in their brains, researchers from the Perelman School of Medicine at the University of Pennsylvania found that amyloid-β facilitates the interaction between the plaques and abnormal tau. This relationship promotes the spread of mutated tau proteins in neurons, which is the hallmark of long-term Alzheimer’s disease. They published their findings this week in Nature Medicine.

“Making an AD mouse model that incorporates both Aβ and tau pathologies in a more AD-relevant context has been greatly sought after but difficult to accomplish,” said senior author Virginia M-Y Lee, PhD, director of the Center for Neurodegenerative Disease Research (CNDR) at Penn. “This study is a big step for AD research, which will allow us to test new therapies in a more realistic context.”

Alzheimer’s disease is characterized by Aβ plaques outside cells and clumps of tau within cells. Researchers have proposed that Aβ plaques are the initiating pathology of AD, but the failure of all AD clinical trials based on removing Aβ challenges this hypothesis and the idea of targeting Aβ alone to treat AD. At the same time, evidence from other studies, including research from CNDR, strongly correlates the spread of tau clumps with worsening cognition in AD, but the exact link between the two pathologies has remained enigmatic.

Tau works like railroad track crossties in stabilizing microtubules in axons responsible for transporting material inside neurons. Removal of tau protein from microtubules due to its clumping in nerve cells causes the affected neurons to become dysfunctional, ultimately leading to their death and AD.

The Penn team mimicked the formation of three major types of AD-relevant tau pathology in their new mouse model: neurofibrillary tangles, neuropil threads, and tau aggregates surrounding Aβ plaques, called neuritic plaque tau. “For the first time we could see and study the tau clumps in dystrophic axons surrounding Aβ plaques in a mouse model, just like we see in a human brain with AD,” said first author Zhuohao He, PhD, a postdoctoral fellow in Lee’s lab.

The team found that Aβ plaques create an environment that facilitates the rapid amplification and spread of pathological tau into large aggregates, initially appearing as neuritic plaque tau. This was followed by the formation and spread of neurofibrillary tangles and neuropil threads to other neurons. These tau protein formations also impaired brain functions, including memory difficulties, in the mice.

This study is the basis for a new way to explain how the Aβ plaque environment accelerates the spread of tau pathology in the brains of AD patients, which is consistent with imaging studies and investigations of postmortem AD brains.

The findings suggest new targets and strategies to treat AD patients. “Our new mouse model of AD with both Aβ and tau can now be used to test therapies that target one or both pathologies to see if combination or single-target therapy is better,” Lee said.


Explore further:
More human-like model of Alzheimer’s better mirrors tangles in the brain

More information:
Amyloid-β plaques enhance Alzheimer’s brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation, Nature Medicine (2017). nature.com/articles/doi:10.1038/nm.4443

Journal reference:
Nature Medicine

Provided by:
Perelman School of Medicine at the University of Pennsylvania

Tagged with:

About author

Related Articles