This study systematically elucidated the multidimensional pathological features of the pineal gland during ageing and AD progression, finding progressive calcification, sexual dimorphism in molecular changes, and elevated Aβ and P-Tau deposition alongside cellular depletion and reduced melatonin in Alzheimer's disease.
Key Findings
Results
Pineal calcification was initiated as early as age 3 and showed progressive accumulation with accompanying cellular loss during ageing.
54 total human pineal gland specimens were collected and analyzed histopathologically.
47 specimens were categorized into five age groups: 0–20, 21–40, 41–60, 61–80, and 81–100 years.
Calcification onset was detected as early as age 3.
Progressive accumulation of calcification was accompanied by cellular loss across age groups.
Results
Sexual dimorphism was observed in the pineal gland, with female-predominant patterns including lipofuscin deposition and pineal cysts, and male-predominant characteristics including GFAP immunoreactivity and connective tissue expression.
Lipofuscin deposition was identified as a female-predominant feature.
Pineal cysts were identified as a female-predominant feature.
Glial fibrillary acidic protein (GFAP) immunoreactivity was identified as a male-predominant characteristic.
Connective tissue expression was identified as a male-predominant characteristic.
The authors described this as 'a remarkable degree of sexual dimorphism.'
Results
Amyloid-beta (Aβ) deposition in the pineal gland was positively correlated with age and was markedly elevated in individuals with Alzheimer's disease.
Aβ deposition was detected within the pineal gland tissue.
Phosphorylated Tau (P-Tau) was also detected within the pineal gland.
Aβ deposition showed a positive correlation with age across the five age groups.
Aβ levels were markedly elevated in the AD group compared to controls.
7 cases with confirmed AD-related neuropathological changes were compared to 7 matched controls.
Results
Individuals with Alzheimer's disease exhibited marked pineal cellular depletion and elevated GFAP expression compared with matched controls.
The AD group consisted of 7 cases with confirmed AD-related neuropathological changes matched to 7 controls.
Pineal cellular depletion was described as 'marked' in the AD cohort relative to controls.
GFAP expression was elevated in the AD group compared to controls.
Histopathological analyses were used to assess cellular and molecular changes.
Results
Cerebrospinal fluid analysis revealed significantly reduced melatonin levels in the Alzheimer's disease cohort.
Melatonin levels were measured in cerebrospinal fluid (CSF) samples.
Melatonin was described as 'significantly reduced' in the AD cohort.
This finding was reported alongside structural and molecular changes in the pineal gland in AD.
Li M, Xie H, Li J, Shen Y, Cai L, Lu M, et al.. (2026). The pineal gland in ageing and alzheimer's disease: age-related molecular changes.. Brain structure & function. https://doi.org/10.1007/s00429-026-03072-1