Looking back, looking ahead

This week's issue of the ALZForum carried a long but very interesting article on the state of affairs in Alzheimer's research.  It reviewed important things that happened during 2019 with implications for what's ahead in 2020.  A few highlights:

• In the United States, government funding for Alzheimer's research was increased to $2.8 billion.  This is close to what the National Institute of Health believes is required to find an effective cure for the disease.  (The US is spending more than any other country on Alzheimer's research, but someone at a conference I attended said that China is #2.  I haven't been able to corroborate that because information on Alzheimer's funding internationally seems to be pretty scant.)
• The article reviewed the aducanumab drama.  Excitement around aducanumab raised hope that it and several other drugs will clean the brain of amyloid plaques and  in so doing may improve cognition and slow the progress of Alzheimer's disease -- if administered in large enough doses.  Will the FDA approve it?  Do we really understand how well it works?  What additional trials will be required?  Stay tuned.
• The article sought to dispel the common belief that Alzheimer's research is focused on the amyloid hypothesis we discussed in Beating the Dementia Monster.  The article listed several other strategies that researchers are pursuing.  It thus emphasized the broad fronts in this war.
• The article discussed new insights in the role of genetics in identifying those susceptible to Alzheimer's disease.  When we think of the role of genetics in the disease pathology, we first look for genes, like Apoe4, that can be directly linked and implicated.  But there is a whole host of other genes for which Alzheimer's may be a secondary consequence.  For example, genes that predispose to heart disease or diabetes can indirectly lead to Alzheimer's disease through these other diseases.  Researchers are finding ways to more accurately profile someone's risk by analyzing a person's whole genome.
• The relationship between beta amyloid and pathological tau protein was clarified.  For a long time it was thought that an important cause of cognitive impairment was amyloid plaques interfering with the flow on information between neurons.  However, after several years of steady buildup of the plaques, there is a sudden explosion of amyloid which appears to prompt the appearance of the famous tau tangles.  It is now thought that it may be the tau tangles that are impairing cognition.
• Microglia got a lot of attention this year.  The brain exists largely outside the body's immune system, so microglia are the brain's own immune system.  One idea pursued this year and into 2020 is that a role of properly functioning microglia is to rid the brain of both amyloid plaques and tau tangles.  So some kind of failure of the microglia may be part of the Alzheimer's pathology.
• There was a lot of progress in finding new biomarkers for Alzheimer's disease, such as by using blood tests.  We discussed this several times, including September 2018 and February 2019.  These blood tests measured traces of amyloid in the blood, but new research last year explored blood tests for pathologic tau protein.  This might give evidence of Alzheimer's disease well before there's any evidence amyloid.
• There were some breakthroughs in brain imaging in which PET scans could more clearly identify buildup of tau protein and beta amyloid -- and distinguish between them.
• There was new interest in the role that infection might play in the genesis of Alzheimer's disease, notably with the herpes virus.  We discussed this in June 2018.
• Exercise.  Yes, the idea that vigorous physical exercise protects against and treats Alzheimer's disease got new momentum.
• As we discussed in November 2019, there is a new understanding developing about the role of sleep, especially deep sleep, in Alzheimer's disease.  Apparently the type of brain waves seen in deep sleep can cause rhythmic pulses in the brain that prompt the movement of cerebrospinal fluid (CSF).  The movement of the CSF likely sweeps beta amyloid and tau tangles out of the brain.  This may be why poor sleep plays a prominent role in Alzheimer's pathology.