Study: Alzheimer’s and PMDD
A 2025 study in Frontiers in Endocrinology argues that PMDD and Alzheimer’s disease may share several important biological pathways — especially in women’s brains. The authors do not claim that PMDD causes Alzheimer’s. Instead, they suggest something more nuanced and potentially important: PMDD may be a marker of long-term neurobiological vulnerability in some women.
That idea matters because women make up roughly two-thirds of Alzheimer’s patients, yet female-specific risk factors remain understudied. PMDD may be one of them.
The Study at a Glance
The paper is a review article, meaning it does not present new clinical trial data. Instead, the authors analyzed existing research to explore whether PMDD and Alzheimer’s disease overlap at the biological level.
The central argument is that PMDD and Alzheimer’s may share disruptions in five major systems:
Estradiol
Allopregnanolone
GABA signaling
Serotonin signaling
APOE ε4 genetic risk
Together, these systems affect mood, memory, inflammation, neuroplasticity, and the brain’s ability to adapt to hormonal change.
The hormone connection: Estradiol and brain vulnerability
Estradiol, a form of estrogen, plays a major role in brain function. It supports memory, learning, synaptic plasticity, and hippocampal health. In Alzheimer’s disease, prolonged estradiol decline after menopause may contribute to cognitive vulnerability. In PMDD, rapid estradiol shifts trigger mood and cognitive symptoms in sensitive individuals.
The authors also discuss estrogen receptor genes, especially ESR1 and ESR2. Variants in these genes may affect how the brain responds to estradiol. Some studies have linked estrogen receptor polymorphisms to both PMDD and Alzheimer’s risk, suggesting a possible shared pathway.
Put simply: the same hormone system that helps regulate mood across the menstrual cycle may also shape long-term cognitive aging.
Allopregnanolone: A key neurosteroid in PMDD and Alzheimer’s
The review places special emphasis on allopregnanolone, often abbreviated as ALLO. ALLO is a neurosteroid made from progesterone. It acts on GABA-A receptors, which help calm the nervous system. In theory, ALLO should have soothing, anti-anxiety, antidepressant, and neuroprotective effects. But in PMDD, the brain may respond abnormally to changes in ALLO (See “The biology of PMDD” for more). ALLO is also relevant to Alzheimer’s research. The review describes evidence that ALLO may reduce amyloid-beta production, lower microglial activation, regulate cholesterol pathways, and support neurogenesis.
GABA: When the brain’s brake system malfunctions
GABA is the brain’s main inhibitory neurotransmitter. It functions like a brake system, helping regulate excitability in neural circuits.
The review argues that both PMDD and Alzheimer’s involve problems with excitatory/inhibitory balance. In Alzheimer’s, GABAergic dysfunction may contribute to excessive neuronal activity and cognitive decline. In PMDD, GABA system instability may contribute to mood swings, irritability, anxiety, sensory sensitivity, and cognitive symptoms.
The authors note that in Alzheimer’s disease, major GABAergic neuronal subpopulations — including parvalbumin-positive and somatostatin-positive interneurons — account for about 70% of the relevant GABAergic interneuron population studied in the AD brain. Dysfunction in these systems can disrupt memory circuits and emotional regulation.
This is one of the review’s strongest conceptual links: PMDD and Alzheimer’s may both involve brains that struggle to maintain stable neural regulation under biological stress.
Serotonin: Mood, cognition, and inflammation
Serotonin is already central to PMDD treatment. Serotonin dysfunction may also matter in Alzheimer’s disease. Serotonin receptors are involved in mood, cognition, stress response, inflammation, and excitatory/inhibitory balance. The authors focus on several receptor subtypes, including 5-HT1A, 5-HT2A, 5-HT3A, and 5-HT6A.
One particularly interesting brain region is the basolateral amygdala, which helps regulate emotion and behavior. The review notes that basolateral amygdala dysfunction has been observed in PMDD and may also be relevant to early Alzheimer’s-related anxiety and emotional symptoms.
This raises an important possibility: mood symptoms are not always separate from neurodegenerative risk. In some cases, they may be early signs of shared brain circuitry under strain.
PMDD, depression, inflammation and Alzheimer’s
One of the review’s most provocative arguments is a possible pathway:
PMDD → major depressive disorder → Alzheimer’s disease
The authors note that PMDD and major depressive disorder overlap clinically and biologically. Both involve mood symptoms, stress-system activation, and inflammation. They cite research suggesting that 7 out of every 8 women diagnosed with PMDD developed major depressive disorder within two years.
The inflammation findings are also striking. In a PMDD rat model, researchers found elevated inflammatory markers in the basolateral amygdala. The same kinds of inflammatory pathways are also implicated in depression and Alzheimer’s disease.
The authors suggest that PMDD may act as an “inflammatory initiator” in some women, contributing first to mood disorder vulnerability and later, perhaps, to neurodegenerative risk.
Again, this is a hypothesis — not proof. But it is a biologically plausible one.
APOE ε4: A genetic risk factor worth watching
The review also discusses APOE ε4, the strongest known genetic risk factor for sporadic Alzheimer’s disease.
Women who carry APOE ε4 appear to be at especially high risk for Alzheimer’s. The review notes that female APOE ε4 carriers may show higher Alzheimer’s-related biomarkers in cerebrospinal fluid, reduced hippocampal volume, and greater vulnerability to amyloid and tau pathology.
The authors propose that APOE ε4, estradiol sensitivity, and PMDD may interact. In other words, women with PMDD who also carry APOE ε4 may represent a subgroup at elevated risk — not because PMDD automatically leads to Alzheimer’s, but because both conditions may reflect shared sensitivity in hormone-brain-immune systems.
This is an area where much more research is needed.
What this study does not prove
This review is important, but it should not be overstated. It does not prove that PMDD causes Alzheimer’s disease. It does not show that women with PMDD will develop Alzheimer’s. It does not establish PMDD as an independent Alzheimer’s risk factor.
What it does show is that PMDD and Alzheimer’s may share biological pathways that deserve serious investigation.
The authors explicitly call for longitudinal studies, prospective clinical follow-up, biomarker tracking, neuroimaging, and mechanistic animal research to determine whether women with PMDD show different cognitive aging trajectories or early Alzheimer’s biomarkers.
Why This Matters
For too long, PMDD has been minimized as a menstrual complaint rather than studied as a serious brain-based disorder. This review pushes the conversation in a different direction. It suggests that PMDD may be part of a broader female neuroendocrine vulnerability — one involving hormone sensitivity, neurotransmitter instability, inflammation, depression risk, and possibly cognitive aging.
That does not mean every woman with PMDD should panic about Alzheimer’s. But it does mean PMDD should be taken seriously: medically, scientifically, and socially.
Women with severe PMDD deserve more than symptom management. They deserve research that follows them over time, measures biological markers, tracks cognitive outcomes, and asks whether reproductive mood disorders tell us something important about women’s long-term brain health.
READ THE STUDY: Yang J, Cheng M, Jiang Z, Du C, Zhao J, Luo Z, Zhang Z. “Premenstrual dysphoric disorder as a potential predisposing factor for Alzheimer's disease: a review.” Front Endocrinol (Lausanne). 2025 Oct 14;16:1580947. doi: 10.3389/fendo.2025.1580947.
