Aging & Longevity

The pineal gland in ageing and alzheimer's disease: age-related molecular changes.

TL;DR

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

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.

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.'

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.

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.

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.

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Citation

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