Transcriptomic analysis of probable asymptomatic and symptomatic alzheimer brains

Topic: Amyloid, tau and blood-test diagnosis

Individuals with intact cognition and neuropathology consistent with Alzheimer's disease (AD) are referred to as asymptomatic AD (AsymAD). These individuals are highly likely to develop AD, yet transcriptomic changes in the brain which might reveal mechanisms for their AD vulnerability are currently unknown. Entorhinal cortex, frontal cortex, temporal cortex and cerebellum tissue from 27 control, 33 AsymAD and 52 AD human brains were microarray expression profiled. Differential expression analysis identified a significant increase of transcriptomic activity in the frontal cortex of AsymAD subjects, suggesting fundamental changes in AD may initially begin within the frontal cortex region prior to AD diagnosis. Co-expression analysis identified an overactivation of the brain "glutamate-glutamine cycle", and disturbances in the brain energy pathways in both AsymAD and AD subjects, while the connectivity of key hub genes in this network indicates a shift from an already increased cell proliferation in AsymAD subjects to stress response and removal of amyloidogenic proteins in AD subjects. This study provides new insight into the earliest biological changes occurring in the brain prior to the manifestation of clinical AD symptoms and provides new potential therapeutic targets for early disease intervention.

Key findings

• Differential expression analysis identified a significant increase of transcriptomic activity in the frontal cortex of AsymAD subjects, suggesting fundamental changes in AD may initially begin within the frontal cortex region prior to AD diagnosis.

Why it matters

Comparing brain tissue from people with asymptomatic Alzheimer's pathology, symptomatic Alzheimer's and controls, this study found increased transcriptomic activity in the frontal cortex of asymptomatic cases and disturbances in energy pathways in both groups. It points to possible early biological changes and potential targets, but it is tissue analysis and does not test any treatment.

New to this subject? Start with our plain-English guide: Brain scans & tests →

Study details

• Evidence strengthLow

Read the original

• DOI: 10.1016/j.bbi.2019.05.009
• PubMed: 31063847
• Original source →
• Free full text: Brain Behavior and Immunity →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

@article{patel2019-31063847,
  author  = {Patel, H. and Hodges, A. K. and Curtis, C. and Lee, S. H. and Troakes, C. and Dobson, R. J. B. and Newhouse, S. J.},
  title   = {{Transcriptomic analysis of probable asymptomatic and symptomatic alzheimer brains}},
  journal = {Brain, behavior, and immunity},
  year    = {2019},
  doi     = {10.1016/j.bbi.2019.05.009},
  pmid    = {31063847},
  url     = {https://doi.org/10.1016/j.bbi.2019.05.009}
}

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Integrated genomic approaches identify major pathways and upstream regulators in late onset Alzheimer's disease Scientific reports · 2015-07-23 · usefulness score 64/100 · TREM2 and immune genetics
• Consensus Recommendations for the Postmortem Diagnosis of Alzheimer’s Disease Neurobiology of Aging · 1997-07-01 · usefulness score 49/100 · Brain tissue and pathology
• TYROBP in Alzheimer's disease Molecular neurobiology · 2014-07-23 · usefulness score 42/100 · TREM2 and immune genetics

Related studies in Brain scans and imaging

• Bile acid synthesis, modulation, and dementia: A metabolomic, transcriptomic, and pharmacoepidemiologic study PLoS medicine · 2021-05-27 · usefulness score 67/100
• Differential default mode network trajectories in asymptomatic individuals at risk for Alzheimer's disease Alzheimer's & dementia : the journal of the Alzheimer's Association · 2019-05-18 · usefulness score 59/100
• The Cortical Signature of Alzheimer's Disease: Regionally Specific Cortical Thinning Relates to Symptom Severity in Very Mild to Mild AD Dementia and is Detectable in Asymptomatic Amyloid-Positive Individuals Cerebral Cortex · 2008-07-16 · usefulness score 58/100
• CSF complement proteins are associated with early tau pathology and synaptic damage in an asymptomatic population at risk of Alzheimer’s disease bioRxiv · 2026-08-27 · usefulness score 16/100
• Normative transcriptomic clues to thalamic developmental vulnerability in C9orf7 2-FTLD medRxiv · 2026-10-13 · usefulness score 16/100
• Glial Transcriptomic Convergence in Alzheimer’s and Parkinson’s Disease with Independent Retinal and Aqueous-Humor Evidence Preprints.org · 2026-09-30 · usefulness score 16/100

Similar studies

• Single-cell transcriptomic analysis of Alzheimer’s disease 2019 · Disease mechanisms
• Biomarkers for early detection of Alzheimer pathology 2008 · Brain scans and imaging
• Transcriptomics and mechanistic elucidation of Alzheimer's disease risk genes in the brain and in vitro models 2015 · TREM2 and immune genetics
• Prediction Of Alzheimer Patients with Machine Learning Algorithms 2025 · Genetics
• The genetics of Alzheimer's disease 2014 · TREM2 and immune genetics
• Genetics of Alzheimer's disease 2014 · TREM2 and immune genetics

More on Brain scans and imaging

• A review that covers this ground Mechanisms of lower oesophageal sphincter incompetence in patients with symptomatic gastrooesophageal reflux Gut · 1988-08-01 · usefulness score 84/100
• Newest in this subject Large-scale head-to-head comparison of on- and off-target profiles of [18F]Tauvid and [18F]MK6240 tau-PET in aging and Alzheimer’s disease Research Square · 2026-11-01 · Preprint — not yet peer-reviewed · usefulness score 16/100
• Newest in this subject Repetitive negative thinking is associated with amyloid accumulation over 3 years in cognitively healthy adults medRxiv · 2026-10-31 · Preprint — not yet peer-reviewed · usefulness score 16/100

See all studies in Brain scans and imaging →