Unlocking the secrets of diseased brains
Neuropathologist has found intriguing links between Alzheimer’s and concussions
Dr. Lili-Naz Hazrati is a neuropathologist, a medical specialty that involves examining and diagnosing dead and diseased brain tissue.
And she joined the field mainly for the access it would grant her to this gory stuff.
Because even with recent and prodigious advances in head-scanning technologies, many ailments of this cardinal organ can be diagnosed only after death.
And the hundreds of dead brains she’s examined over more than a decade have given Hazrati fresh and promising ideas about some of today’s most pressing neurological ailments.
“Most neurological diseases . . . they give them a diagnosis during life, but the ultimate final diagnosis is really based on the autopsy still,” says Hazrati, an assistant professor in laboratory medicine at the University of Toronto.
“And in order to understand these diseases we don’t understand, we have to classify them properly.”
For example, the proper classification of various forms of dementia — which can be hard to tell apart on the basis of people’s symptoms when they’re alive — can only be based on the hallmark differ- ences found in their brains after death.
Hazrati’s work has increasingly focused on dementias caused by Alzheimer’s disease and athletic concussions, two of the most worrisome ailments of our times.
And groups of patients who suffer from these conditions — or their families — have agreed to donate their brains to her medical research.
Dozens of times a year, a pager she faithfully carries will go off, alerting her to the fact one of these patients has died.
And Hazrati, a horror movie aficionado, will either rush off herself or arrange for a colleague to retrieve the brain and send it to her lab.
“The autopsy will then allow me to classify (the diseases) properly,” says Hazrati, who works out of the University Health Network’s Toronto General site.
It was during her classifications of Alzheimer’s victims and concussionbased chronic traumatic encephalopathy (CTE) patients — the latter mostly former athletes — that Hazrati noticed something striking.
While she found that the brains of older CTE patients closely resembled those of Alzheimer’s victims, the brains of younger concussed athletes did not.
What these younger athletes did have was widespread damage and destruction of the brain’s glia cells, which surround and help protect the working neurons that allow for movement, emotion and thought.
As a result, Hazrati theorized that the progression to the advanced forms of both diseases might follow similar routes and — more important — have a common cause in these supporting glia cells.
And, as it turns out, she found that the same glia cell receptors that were activated by injury and inflammation in concussed human brains could be triggered to kick off the degenerative process in mice models of Alzheimer’s disease.
Thus, Hazrati says, the telltale signs of Alzheimer’s disease — the so-called plaques and tangles that stuff the withered neuron cells of its victims — may not be a cause but an end product of changes that originate in surrounding glia cells.
And the triggering receptors within these supporting cells may prove an exciting target for new drug development and a potential source of biomarkers for early diagnosis and risk-level assessments for both conditions.
A mother of two girls, 11 and 13, Hazrati’s interest in the brain dates back to a summer job she happened upon at Quebec City’s Laval University when she was a teenager.
“I was just starting biology and I heard from somebody else in the cafeteria that there was this job in a lab for the summer,” the Iranian native says.
“I was in this dark room for the whole summer projecting these slides of (the brain structures called) basal ganglia on the wall.
"You become emotionally attached to this work. It became my world, basically.”
Indeed, by the time Hazrati completed her undergrad science degree, she’d already done enough brain research during summer stints at the brain lab to write a quick master’s thesis.
She went on to gain a PhD in neuroscience and did several post-doctoral fellowships before attending medical school at the University of Montreal.
Hazrati hopes that 2015 will allow her to solidify her work on the Alzheimer’sconcussion connection.
“We really need to go forward and to spend a good year of concentrated research comparing all these hypotheses and doing more experiments on this.”