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22 THE BRANDON SUN • HEALTH • WEDNESDAY, SEPTEMBER 25, 2019

Scientists diversify Alzheimer’s drug search

WASHINGTON — When
researchers at the University of
Kentucky compare brains do-
nated from people who died
with dementia, very rarely do
they find one that bears only
Alzheimer’s trademark plaques
and tangles — no other dam-
age.
If they do, “we call it a uni-
corn,” said Donna Wilcock, an
Alzheimer’s specialist at the
university’s aging centre. Con-
trary to popular perception,
“there are a lot of changes that
happen in the aging brain that
lead to dementia in addition to
plaques and tangles.”
That hard-won lesson helps
explain how scientists are re-
thinking Alzheimer’s.
For years, researchers have
been guided by one leading
theory — that getting rid of
a buildup of a sticky protein
called amyloid would ease the
mind-robbing disease. Yet drug This Aug. 14, 2019 photo provided by the University of Kentucky shows brain samples in storage at the Sanders-Brown
after drug has failed. They Center on Aging in Lexington, Ky. Once a month, researchers at the University of Kentucky gather to compare donated
might clear out the gunk, but brains from people who died with dementia. Very rarely do they find one that bears only Alzheimer’s trademark plaques
they’re not stopping Alzhei-
mer’s inevitable worsening. and tangles, no other damage. (Mark Cornelison/University of Kentucky via AP)
The new mantra: diversify. drugs are in the earliest research dementia. ington University in St. Louis
With more money — the stages. It’s far from clear that So something else — may- took a closer look — and says
government had a record $2.4 any will pan out, but “the field be several other things — also microglia may be key to how
billion to spend on Alzheimer’s is now much more open-mind- must play a role. One possible the amyloid-tau duo turns tox-
research this year — the focus ed than it ever was to alterna- culprit: The brain’s unique im- ic.
has shifted to exploring multiple tive ideas,” Wilcock said. mune cells, called microglia In donated human brains,
novel ways of attacking a disease (my-kroh-GLEE’-ah). his team found more tau tan-
now considered too complex for BREAKING THE PLAQUE No surprise if you’ve never gles clustered around amyloid
a one-size-fits-all solution. On AND TANGLE LINK heard of microglia. Neurons plaques when people harboured
the list, researchers are targeting No one knows what causes are the brain’s rock stars, the microglia-weakening TREM2
the brain’s specialized immune Alzheimer’s but amyloid de- nerve cells that work together mutations. The researchers al-
system, fighting inflammation, posits were an obvious first sus- to transmit information like tered the TREM2 gene in mice
even asking if simmering infec- pect, easy to spot when exam- memories. Microglia are part of and seeded their brains with a
tions play a role. ining brain tissue. But it turns a different family of cells long little human tau. Sure enough,
Some even are looking be- out that gunk starts silently regarded as the neurons’ sup- more tangles formed next to
yond drugs, testing if electri- building up 20 years before any port staff. But “it’s becoming plaques in mice with weak
cal zaps in the brain, along a memory loss, and by itself it’s clear they’re much more active microglia than in those with
corridor of neural connections, not enough to cause degener- and play a much more signif- functional immune cells, they
might activate it in ways that ation. icant role,” said Dr. Richard recently reported in Nature
slow Alzheimer’s damage. Sometime after plaques ap- Hodes, director of the National Neuroscience.
Tuesday, doctors at Barrow pear, another protein named Institute on Aging. Why? Normal microg-
Neurological Institute in Phoe- tau starts forming tangles in- One microglial job is to gob- lia seem to restrict amyloid
nix announced they had im- side neurons, heralding cell ble up toxic proteins and cellu- plaques, which limits damage
planted a pacemaker-like “deep death and memory loss. lar debris. Recently, a mutation to surrounding tissue — dam-
brain stimulation” device into But again, not always: Au- in a gene called TREM2 was age that can make it easier for
the first of more than 200 pa- topsies show sometimes people found to weaken microglia and tau to take hold, he explained.
tients for an international study. die with large amounts of both increase the risk of Alzheimer’s.
Most of the fresh starts for plaques and tangles, yet escape Dr. David Holtzman at Wash- » Continued on Page 23