The Brain Plaques and Tangles That Cause Alzheimer’s

The Brain Plaques and Tangles That Cause Alzheimer’s

Meryl Comer: The mainstream research has been focused on beta amyloid.  Tau has always been there, but now there is a big controversy about where the progression comes, where does it really lie?  Take that debate on Dr. Gandy. 

Dr. Gandy:  Well certainly people with Alzheimer’s disease have two sorts of lesions in their brains, two sorts of clumps of protein.  Some of these clumps are in between nerve cells, and others are inside nerve cells.  The ones that are in between the nerve cells are called amyloid plaques.  The clumps that are inside the nerve cells, which are twisted, are called tangles or neurofibrillary tangles.  Now for many years we didn’t sort of know what the sequence of events was, but it is very clear now that all the genes that cause Alzheimer’s disease point to the buildup of amyloid. So it appears that Alzheimer’s disease amyloid comes first and tangles come next.  They may be extremely important in understanding why the nerve cell dies.  Now the disease that Dr. Troncoso mentioned, frontal temporal dementia, has also helped us to understand the relationship between plaques and tangles because in that disease the mutations that cause the genetic forms are in the protein called tau that builds up and causes tangles.  People with frontal temporal dementia get tangles, but they never get plaques, so in Alzheimer’s disease plagues can cause tangles, but in frontal temporal dementia tangles don’t cause plaques.

Meryl Comer: Well why is it so hard these days to get a grant from NIA around beta amyloid when you can get it for tau?

Dr. Gandy:  Well so there is a specific reason for that that’s really evolved a lot in the last year.  There is a study that was reported this spring that showed using an antibody, a chemical aimed at the amyloid substance... that if people with mild Alzheimer’s disease received antibody infusions, anti-amyloid infusions, for a year and a half that the amyloid buildup in their brains would go down by about 25%.  They didn’t change at all clinically.  They didn’t get any better in terms of their cognitive function.  Why is that? Because we didn’t start early enough, because we didn’t treat long enough or because it’s actually another form of amyloid, not the plaques, but these floating clumps called oligomers?

Meryl Comer:  You wanted to make a point, yes, doctor. 

Dr. Troncoso:  Yeah well, I think that there is a lot of debate between the amyloid and tau deposition, but I think one should not get stopped at that point of that argument because it’s perfectly possible that one of these abnormalities, let’s say amyloid may trigger the rest and there is more than amyloid and tau.  We haven’t spoken, but there is a very significant inflammatory, inflammation in the brain that once you have perhaps amyloid and tau trigger that event it becomes self-sufficient.  It actually may even promote more amyloid or more tau deposition, so I think that tau it may be as important as amyloid, but it may be later on in this progression of the disease. And if you could actually target each of these elements it probably would be beneficial. So I don’t see really a tremendous dichotomy, antagonism between looking at amyloid and tau.  I think that both are perfectly legitimate targets of research and one more perhaps disgression in terms of the dementia that is being seen in patients who have head trauma.  Most of that, the lesions that they have is of the tau type, so I think both of these targets amyloid and tau should be addressed.  There is no reason to eliminate one of them.

Dr. Gandy:  There is the one experiment to mention that might also explain why the shift sort of toward tau.  A lot of what we’ve learned about Alzheimer’s disease is from mouse models.  Mice normally never ever get Alzheimer’s disease because their amyloid is different enough that it doesn’t clump and build up.  If we then put into a mouse the gene for amyloid and with a mutation that would cause it to build up and the gene for tau so that it will get tangles, then as that animal ages it will get buildup of plaques and tangles just like, similar to humans with Alzheimer’s disease.  They will then lose their ability to find their way around their cage or to find their way around a swim maze.  If you then treat them with a drug or substance that will decrease the levels of tau, will lower the tau down, the cognitive function comes back, so it’s possible to sort of render the amyloid inert if you can turn down the tau at least in the mouse model.

Amyloid plaques and neurofibrillary tangles inside the brain are the best explanation we have for how Alzheimer’s develops.

Are you an overbuyer or an underbuyer?

One way to limit clutter is by being mindful of your spending.

Videos
  • Overbuyers are people who love to buy — they stockpile things as a result. These are individuals who are prone to run out of space in trying to store their stuff and they may even lose track of what — and how much of what — they have.
  • One way overbuyers can limit their waste, both money and space wise, is by storing items at the store, and then buy them when they really need them.
  • Underbuyers tend to go to extraordinary lengths to not buy things. They save money and do fewer errands, however, they often make do with shabby personal items. They may also, when they finally decide to go out to buy a product, go without entirely because the item may no longer be available.

Five Hawks Down: watch the tragic migration of six Californian raptors

Tracking project establishes northern Argentina is wintering ground of Swainson's hawks

Image: @TrackingTalons / Ruland Kolen
popular
  • Watch these six dots move across the map and be moved yourself: this is a story about coming of age, discovery, hardship, death and survival.
  • Each dot is a tag attached to the talon of a Swainson's Hawk. We follow them on their very first migration, from northern California all the way down to Argentina.
  • After one year, only one is still alive.

Discovered: destination Argentina

Image: @TrackingTalons

Young Swainson's hawks were found to migrate to northern Argentina

The Buteo swainsoni is a slim, graceful hawk that nests from the Great Plains all the way to northern California.

It feeds mainly on insects, but will also prey on rodents, snakes and birds when raising their young. These learn to fly about 45 days after hatching but may remain with their parents until fall migration, building up flying skills and fat reserves.

A common sight in summer over the Prairies and the West, Swainson's hawks disappear every autumn. While it was assumed they migrated south, it was long unclear precisely where they went.

A group of researchers that has been studying raptors in northern California for over 40 years has now established exactly where young Swainson's hawks go in winter. The story of their odyssey, summarised in a 30-second clip (scroll down), is both amazing and shocking.

Harnessing the hawks

Image: @TrackingTalons, found here on imgur.

A Swainson's hawk, with tracking device.

The team harnessed six Swainson's hawks in July, as they were six weeks old and just learning to fly. The clip covers 14 months, until next August – so basically, the first year of flight.

Each harness contains a solar-powered tracker and weighs 20 grams, which represents just 3% of the bird's body weight. To minimise the burden, only females were harnessed: as with most raptors, Swainson's hawk females generally are bigger than males.

The first shock occurs just one month (or about 2.4 seconds) from the start of the clip: the first dot disappears. The first casualty. A fledgling no more than two months old, who never made it further than 20 miles from its nest.

By that time, the remaining five are well on their way, clustering around the U.S.-Mexico border in Texas. Swainson's hawks usually travel at around 40 mph (65 km/h) but can almost double that speed when they're stooping (i.e. dive down, especially when attacking prey).

'Migration unrest'

There's a strong genetic component to migration. As usual, the Germans have nice single word to summarise this complex concept: Zugunruhe ('tsook-n-roowa'), literally: 'migration unrest' (1). It denotes the seasonal urge of migratory animals – especially birds – to get on their way. Zugunruhe exhibits especially as restless behaviour around nightfall. The number of nights on which it occurs is apparently higher if the distance to be travelled is longer.

The birds may have the urge to go south, but genetics doesn't tell them the exact route. They have to find that out by trial and error. Hence the circling about by the specimens in this clip: they're getting a sense of where to find food and which direction to go. Their migratory paths will be refined by experience – if they're lucky enough to survive that long.

Each bird flies solo: their paths often strongly diverge, and if they seem to meet up occasionally, that's just an illusion: even when the dots are close together, they can still be dozens if not hundreds of miles apart.

Panama snack stop

Image: @TrackingTalons

The Central American isthmus is a major bird migration corridor

They generally follow the same route as it is the path of least resistance: follow mountain ranges, stay over land. Like most raptors, Swainson's hawks migration paths are land-based: not just so they can roost at night, but mainly to benefit from the thermals and updrafts to keep them aloft. That reduces the need to flap wings, and thus their energy spend – even though the trip will take longer that way.

As this clip demonstrates, the land-migration imperative means the Central American isthmus is a hotspot for bird migration. Indeed, Panama and Costa Rica are favourite destinations for bird watchers, when the season's right. A bit to the north, Veracruz in Mexico is another bird migration hotspot.

It's thought most hawks don't eat at all on migration. This clip shows an exception to that rule: on the way back, one bird takes an extended stopover of a couple of weeks in Panama, probably spending its time there foraging for food.

So, when they finally arrive in northern Argentina, after 6 to 8 weeks' migration, the hawks are pretty famished. Until a few decades ago, they fed on locusts. For their own reasons, local farmers have been getting rid of those. The hawks now concentrate on grasshoppers, and basically anything else that's edible.

For first-time visitors, finding what they need is not easy. Three of the five dots go dark. These birds probably died from starvation. But two birds thrive: they roam the region until winter rears its head in South America, and it's time to head back north again, where summer is getting under way.

Both dots make it back across the border, but unfortunately, right at the end of the clip, one of the surviving two birds expires.

Harsh, but not unusual

Image: @TrackingTalons, found here on imgur.

This old lady is 27 years old, but still nesting.

While a one-in-six survival rate may seem alarmingly harsh, it's not that unusual. First-year mortality for Swainson's Hawks is between 50% and 80%. Disease, starvation, predators and power lines – to name just a few common causes of death - take out a big number.

Only 10% to 15% of the young 'uns make it past their third or fourth year into adulthood, but from then on, annual survival rates are much better: around 90%. Adult Swainson's Hawks can expect to live into their low teens. There's one documented example of a female Swainson's Hawk in the wild who was at least 27 years old (and still nesting!)

The Californian population of Swainson's Hawks plummeted by about 90% at the end of last century but is now again increasing well. The monitoring project that produced this clip has been going for about four decades but is seeing its funding dry up. Check them out and consider supporting them (see details below).

Image: Yale School of Forestry and Environmental Studies

Migration trajectory of B95, the 'Moonbird'.

Not all migrating birds shun the ocean. Here's an incredible map of an incredible migration path that's even longer than that of the Swainson's hawks.

In February 1995, a red knot (Calidris canutus rufa) in Tierra del Fuego (southern Argentina) was banded with the tag B95. That particular bird, likely born in 1993, was recaptured at least three times and resighted as recently as May 2014, in the Canadian Arctic.

B95 is more commonly known as 'Moonbird', because the length of its annual migration (app. 20,000 miles; 32,000 km) combined with its extreme longevity (if still alive, it's 25-26 years old now) means its total lifetime flight exceeds the distance from the Earth to the Moon.

As many other shorebirds do, the red knot takes the Atlantic Flyway hugging the coastline and crossing to South America via the ocean.

B95 has become the poster bird of conservationists in both North and South America. A book titled Moonbird: A Year on the Wind with the Great Survivor B95 (2012) received numerous awards, B95 has a statue in Mispillion Harbor on Delaware Bay and the City of Rio Grande on Tierra del Fuego has proclaimed B95 its natural ambassador.

Perhaps one day the nameless Swainson's Hawks in this clip, fallen in service of their ancestral instincts – against the odds of human increasing interference – will receive a similar honour.

Migration clip found here at the DataIsBeautiful subreddit. Read through the comments to learn a lot more about Swainson's Hawks, and raptors in general.

Check out the California raptor tracking programme 'Tracking Talons' on Twitter at @TrackingTalons, on their Facebook page, and on their website.

Strange Maps #965

Got a strange map? Let me know at strangemaps@gmail.com.

(1) 'Zug' is a wonderfully polyvalent German word. It can mean: a train, a chess move, a characteristic, a stroke, a draft (of a plan), a gulp (of air), a drag (from a cigarette), a swig (from a bottle), and more.

Trusting your instincts is lazy: Poker pro Liv Boeree on Big Think Edge

International poker champion Liv Boeree teaches decision-making for Big Think Edge.

Big Think Edge
  • Learn to make decisions with the clarity of a World Series Poker Champion.
  • Liv Boeree teaches analytical thinking for Big Think Edge.
  • Subscribe to Big Think Edge before we launch on March 30 to get 20% off monthly and annual memberships.
Keep reading Show less