The pathology of Alzheimer's

Alzheimer's disease is one of those potentially inevitable, maybe preventable, what the heck is really causing it diseases that came on to the medical scene in the 20th century. Essentially, as a person ages the brain atrophies slightly, and in some people they experience age-related memory problems and other cognitive effects of making it through a longer life than previous generations of humans. In other people, pathological changes to the brain induce a more pronounced memory issue that then manifests as dementia - this is Alzheimer's disease.

The disorder is diagnosed based on symptoms because the changes to the brain can't be confirmed until autopsy, showing the protein plaques in the brain tissue and spongy consistency that causes the cognitive changes. Aberrant protein beta-amyloid has long been blamed as the source of the plaques, causing Alzheimer's to be related to prion diseases and spongiform encephalopathies like mad cow, but inappropriate aggregations of naturally occurring tau protein might also be to blame, making the disease more complex and multifactorial.

Neurotangles from ADEAR at the National Institute of Aging

 

 

 

Tau proteins are cytoskeletal proteins involved in the stability of microtubules in neurons. This function makes tau proteins important components of neuron morphology and nerve cell construction. Because of this relationship and the role neuronal morphology (i.e. axons and dendrites) plays in neural networks, changes in tau protein can cause alterations in how neurons interact and the integrity of the nerve cell structure. In pathological conditions tau proteins may self-aggregate (i.e. bind to each other), forming filaments that interrupt the cell structure and intracellular transport.

 

Tau proteins consist of various isorforms due to alternative RNA splicing, varying by which exons are excluded. The RNA transcript is from a single gene. Some forms of tau are expressed more during fetal development or more during adulthood. Tau is also known as neurofibrillary tangle protein, but it gets its name from its full designation – paired helical filament-tau. The gene designation is MAPT or TAU. Phosphorylation of serine and threonine residues at serine-proline and threonine-proline motifs is a normal post-translational modification. The isoforms are also characterized as type I or type II based on the number of repeats in the microtubule-binding domain. This characterstic provides tau two different ways to interact with microtubules.

 

Microtubules are normal cell components made of filaments of tubulin. These cytoskeletal structures have been found to be important in the distal portions of axons. They are also essential for the transport of neurotransmitters from the cell body to the synapse. Thus, disruption of the microtubules can disrupt neurotransmission. Tau protein has been found to be necessary for microtubule assembly and possibly cell polarity. In certain neurodegenerative disorders, such as Alzheimer’s disease, neurofibrillary tangles have been observed, an aberrant and improperly functioning form of the tubulin-tau network.

Diseases caused by mutations in the tau gene on chromosome 17 and/or disruption of the structure and/or function of the tau protein(s) are called tauopathies. A number of neurodegenerative diseases are associated with filamentous tau aggregation, including Alzheimer’s disease and some dementias. Disruption of the cytoskeleton by aggregates can activate degenerative cellular processes that result in neuron loss. Research has found that hyperphosphorylation of tau protein may be the culprit underlying tauopathies. Pathological tau proteins undergo glycation post-translation, and hyperphosphorylated tau is polyubiquitinated, which may trigger degradation by the polysome. In addition, a lack of the molecular chaperones known as heat shock proteins is known to play a role in tau aggregation. However, exactly how tau causes neurodegeneration is not yet known.

 

An extensive review of the tau gene and resulting protein was published in Physiological Reviews in 2004.

 

Nicotine as a gateway drug

Research published earlier this month in the journal Science Translational Medicine reported the effects of nicotine on mice in regards to cocaine use.

The researchers took two sets of mice - one was exposed to nicotine and the other wasn't. Both were then exposed to cocaine. They found that the nicotine-exposed mice were more likely to seek out cocaine again, by a great deal (78%!).

They found that exposure to nicotine caused epigenetic changes (specifically histone acetylation) in genes related to the reward system in the brain, allowing changes in the expression of certain genes during exposure to cocaine, inducing a more addictive experience.

Research has already shown that brain function alters with addiction. But this is one of the first pieces of evidence of genetic mechanisms underlying the "gateway" theory of drug use. Those cigarettes are affecting your brain...via your genes!

Sleep apnea linked with cognitive issues

At the University of California, San Francisco, studies on sleep apnea have found that the presence of the condition in older women predicts memory and cognitive issues 5 years later. One-third of women had dementia or cognitive impairment at the second study date - among those who had sleep apnea at the first study date, 45 percent had dementia or cognitive impairment. The statistics found that older women with sleep apnea are twice as likely to have dementia or memory issues.

Reuters reported on the study yesterday.

Knowing self in short-term memory

An inability to relate to events in the past, to not remember being somewhere or with someone, is a dysfunction of episodic memory. Alzheimer's disease and memory-related dementia  include such a dysfunction, but alcohol abuse can also lead to an inability of the brain to use this metamemory process.

The concept of autonoetic consciousness, a key aspect of episodic memory was developed in the 1970s and expanded upon with brain imaging studies in the past 4 decades. The mechanism involves the concept of self, which is unique to every individual

Read more about the phenomenon of episodic memory.

Symmetric brains in lefties

Ten percent of the human population is left-handed. Over the years this has been attributed to a number of intangible reasons. In recent years, research has shown that handedness, or hand dominance, may stem from the symmetry of the brain during early development. Genes determine this embryonic development and a certain genotype switches which hemisphere controls handedness and language skills. But it's even more complex - lefties have more symmetric distribution of language across the brain.

This is your brain on marijuana

The effects of marijuana on the human body are still debated, and anecdotal effects of marijuana use, including euphoria, relaxation, paranoia, memory loss, and hunger, vary among users depending on duration, dosage, and method of use. THC crosses the blood-brain barrier and acts on cannabinoid receptors, which are present in high quantities in areas affecting pleasure, memory, concentration, coordination, and sensory and time perception. Most effects of use are short-lived, but chronic use prolongs the effects for days or weeks after THC has left the bloodstream. The reversibility of long-term effects is unclear.

Marijuana has effects on neurotransmitter uptake, cerebral blood flow, and brain structure, some of which have been inconclusive in research. 

Levels of Brain Injury

Injuries to the brain are sustained when a force impacts the head, either from without or within. For all types and levels of brain injury, the symptoms can include numbness and weakness in the extremities, extreme drowsiness, headache, dizziness, vision problems, slurred speech, vomiting or nausea, loss of consciousness and cognitive issues. Any brain injury can be devastating, whether traumatic or acquired, but the type and level of injury determines treatment and prognosis. Read more about the types and levels of brain injury.

TBI causes brain damage

Traumatic brain injury, commonly known by its acronym TBI, is a type of internal injury sustained from head trauma, including blows to the head and bullet wounds. The type of brain damage sustained from TBI depends on the type and severity of head trauma, including whether it is an open or closed injury. Read more about the types of brain damage resulting from TBI.

Cell phone waves affect the brain

Studies have found no increased risk of cancer associated with cell phone use according to both the American Cancer Society and National Cancer Institute. However, the use of radiofrequencies so close to the head may still have other effects. These yet unknown effects appear to include energy use by brain cells if the findings of a February 2011 study in JAMA are any indication. This energy use isn't greater than other natural activities, but researchers stress the use of hands-free devices just to be safe.