A new study reveals a possible biological reason that Alzheimer's Disease (AD) progresses at different rates in different patients.
The study focused on tau, a protein found in the neurofibrillary tangles in the brain that are a well-known sign of AD.
Tau can undergo a variety of modifications during the course of the disease including phosphorylations. Researchers found that the presence of different forms of phosphorylated tau could explain why the disease has variable effects.
Physicians have long known that, from patient to patient, there can be substantial variation in the clinical presentation of Alzheimer's Disease, including age of onset, rate of memory decline and other clinical measures.
Also, higher levels of pathological tau in the brain are associated with more severe disease. However, there are few clues as to what causes this variation between patients.
This team studied samples from 32 patients who were diagnosed with what is considered "typical AD" while living, and that diagnosis was confirmed after death.
The age at diagnosis and the rate of disease progression varied markedly among these patients.The researchers also conducted an in-depth characterization of the molecular features of tau proteins within the brains of these patients.
This included levels of different species of tau, capacity of tau to induce aggregation (also called seeding), as well as the presence of specific post-translational modifications using biochemical, biophysical and bioactivity assays, as well as advanced mass spectrometry techniques.
The researchers found "striking" variation in the presence of phosphorylated tau oligomers that associates with greater tau spread, and, importantly, worse disease.
Different specific modifications were associated with different degrees of severity and progression rate.
Notably, these specific molecular characteristics led to variable recognition by antibodies which are currently being considered for the therapeutic targeting of tau proteins in AD and associated diseases.
"We speculate that there are different molecular 'drivers' of Alzheimer's progression, with each patient having their own set of these," says senior author of the report and adds that, "this is similar to what we see in cancer, where there are several types of lung or breast cancer, for example, and the treatment depends on the particular molecular drivers in the patient's tumor."
https://www.massgeneral.org/news/press-release/tau-protein
https://www.nature.com/articles/s41591-020-0938-9
Heterogeneity in Alzheimer's disease linked to Tau molecular diversity
- 1,147 views
- Added
Edited
Latest News
Tumor infiltration of immun…
By newseditor
Posted 28 May
New light-controlled 'off s…
By newseditor
Posted 28 May
Gene function during embryo…
By newseditor
Posted 28 May
Formation of 3D blood vesse…
By newseditor
Posted 27 May
Liver regeneration during c…
By newseditor
Posted 27 May
Other Top Stories
Leukemia detection using artificial intelligence
Read more
Protein interactions in kidney cancer
Read more
Brain tumor organoids may be key to time-sensitive treatments for g…
Read more
Importin protein transporting tumor causing catenin to the nucleus…
Read more
How a specific protein regulates tumor growth
Read more
Protocols
SEMORE: SEgmentation and MO…
By newseditor
Posted 26 May
Spatially resolved lipidomi…
By newseditor
Posted 24 May
Efficient expansion and CRI…
By newseditor
Posted 21 May
Massively parallel in vivo…
By newseditor
Posted 20 May
Breast cancer-on-chip for p…
By newseditor
Posted 16 May
Publications
Advanced microbiome therape…
By newseditor
Posted 29 May
Hippocampal astrocytes indu…
By newseditor
Posted 29 May
TNIK's emerging role in can…
By newseditor
Posted 29 May
Diabetes drugs activate neu…
By newseditor
Posted 29 May
Circadian tumor infiltratio…
By newseditor
Posted 28 May
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar