Premium
P4‐002: Cerebral microinfarcts: A systematic review of neuropathological studies
Author(s) -
Bresser Jeroen,
Brundel Ma,
Dillen Jeroen,
Kappelle Jaap,
Biessels GeertJan
Publication year - 2011
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2011.05.2021
Subject(s) - context (archaeology) , dementia , pallor , neuropathology , pathology , medicine , gliosis , vascular dementia , cognitive decline , disease , biology , paleontology
jects). Using laser capture microdissection, we collected neuronal/dendritic fields of CA1 from slide specimens, isolated nucleic acid, and amplified these small samples for quantification by microarray (Affymetrix HG-U133 v2). Results: Across all subjects, mini-mental status exam (MMSE) scores correlated more strongly with gene expression than did neurofibrillary tangle (NFT) counts. However, within the cohort of control and incipient subjects (n 1⁄4 15), NFT identified more genes. Functional grouping analysis revealed a very strong downregulation of neuronal and mitochondrial signatures. In addition to upregulated inflammatory signatures, there was also a strong increase in the expression of genes associated with vascular function. A comparison between transcriptional profiles measured here (neuronal-enriched) with those from prior work (whole tissue) in the same subjects revealed a very strong and significant level of agreement, particularly with inflammatory, neuronal, and mitochondrial signaling. Conclusions: Microarray analysis of archived formalin fixed paraffin embedded samples yields results that are highly comparable to more standard fresh frozen tissue block approaches. Further, isolated dendritic/ neuronal fields of CA1 appear to also contain a previously masked neurovascular signature that correlates with disease progression. Finally, differences in signature between tissue block and microdissected neuronal subfield suggest that regional sampling, rather than tissue preparation or RNA handling, may likely explain differences in results.