Professor Sonia Sharma: Teaches Alzheimer’s in La Jolla.

Dr. Sonia Sharma makes no bones about it: when she’s studying immune diseases like Alzheimer’s and Parkinson’s, she concentrates on women, not men.  She is also one of those vital, loquacious academics who actually likes talking to outsiders about her trade — which from today will, often as not, involve staring through the brand-new multi-million-dollar microscope they have just unpacked here at the LJI lab. (That’s the La Jolla Institute for Immunology.) It feels like there’s a lot of money floating around the research establishment, but with reason: LJI can wrap itself in impressive figures: 35 years old, voted #1 in the world as a research workplace ten years ago, with about 500 researchers and staff — every one, looks like, a PhD. 

I have been asking Dr. Sharma about her insistence on identifying female Alzheimer cases as though she could find differences based on the sex of the blood sample giver. She has been facing some pushback — mainly, it seems, from men. “Looking at any disease under the gender-specific lens does not take anything away from anybody,” she says, here in her lab office. “Wouldn’t you want to know, thinking about male health, if your disease is different from a woman’s, which would mean you get different treatment, and she gets different treatment? And doesn’t that make everybody better?”

Dr. Sharma’s autoimmune casualty figures.

Sharma is one of a team of researchers here at LJI, a place that is all about breakthrough immunology. “We believe no other biomedical discipline has greater implications for human health than immunology,” LJI’s blurb reads. Its researchers study immune-related diseases like asthma, cancer, covid-19, diabetes and Parkinson’s, under the ambitious stated aim of creating a “Life Without Disease.” Sharma has just been made a tenured professor here.

“We like to study metabolites that regulate these diseases,” she says. “By ‘metabolites,’ I mean small molecules in circulation in our blood that can protect us from vascular inflammation. Also, omega-3 polyunsaturated fatty acids that are shown to be brain protective. These are dietary metabolites. Fish oil! We went into this trying to look at it from a gender point of view, because women are two-fold more likely to develop Alzheimer’s than men.”

She studies Alzheimer’s Disease along with the other immune diseases. Her beef?  Women, she says, as the major victims of Alzheimer’s (two-thirds of the five million Americans living with the disease are women) have been ignored as a separate category worth studying by many medical researchers. “Women have different vulnerabilities to AD, and also different protections against it.” Part of the reason for her push, she implies, is that the world of medicine has always been male-dominated, that it doesn’t study women’s immune disease weaknesses and strengths, and that the big bucks still largely fund studies that treat men and women as identical.

Professor Sharma’s stats show men biggest covid victims.

“I’ll give you an example of what we found in our research,” she says. “We did a study of small molecule metabolites — perhaps an amino acid, a fatty acid. And we had women and we had men. We took blood [samples] from them when they had no AD, and then when they developed AD. And what did we find in our analysis? We found that there was a specific group of protective metabolites. Those were metabolites that were high in the blood of women who didn’t have Alzheimer’s, and low in the blood of women who did have Alzheimer’s. We also found that men didn’t have [those protective metabolites] at all.” 

And yet women get Alzheimers more than men?  “It’s counterintuitive. But the women who had had [the supply of protective metabolites] were younger women. Older women were losing it, and the men never had it. So what it looks like is perhaps that younger women have evolved mechanisms to protect themselves against Alzheimer’s. Men lack these protective molecules, and that may leave them vulnerable to developing AD. But men might be also less prone to it. Because it’s established that women have stronger immune systems than men, because they’re having babies, and a lot of viruses interfere with babies’ development. Remember Zika? German measles? HCMV? It causes heart defects. Zika causes microencephaly. Child-bearing women have to have stronger immune systems to protect the developing fetus. This is a known. But they don’t last. But women have higher antibody [counts], higher levels of certain immune cells in their blood, and they’re more responsive to vaccines. Severe covid is a men’s disease, because men are less protected by their immune systems. Women need more protection because we have [monthly cycles], ‘the heat.’ So we women have the protective shield [of our antibody cells]. But if that shield wears off, then as we age, we’re more prone to Alzheimer’s.” (An additional factor: women tend to live longer than men.)

But Alzheimer’s research, Dr. Sharma says, is out of step. “With the majority of experiments that are done, especially in humans but also in mice, folks tend never to take [gender differences] into consideration. We have all this information about the disease, and yet we’re missing half the puzzle. Part of the problem was women not being in high positions [in the medical research establishment], and the [issue of] women’s particular interaction with immune diseases like AD has just not been thought of as important. And now we turn in hindsight and say, ‘Yeah, we have all this important other information about the disease, but we’re missing half of the puzzle.’ But if [somebody got up and said], ‘I’m going to study female mice, and I’m going to study gender differences…’” — she laughs . “It wasn’t something you as a woman would want to say that you were looking at. [The response] would probably be, ‘Okay, why do you want to study something — female response to AD — that’s only happening in half the population?’ And that sounds very [reasonable]. But then you turn around and you say, ‘Wait a minute, no! Why wouldn’t you want to fill in the other 50 percent of the picture? It doesn’t change. Have we cured Alzheimer’s? No! We haven’t. Have we cured cardiovascular disease? No we haven’t. Maybe it’s because we’re not looking at the full picture.”