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amyloid (senile, neuritic) plaque

Microscopic foci of extracellular amyloid deposition observed in patients with Alzheimer's disease, resulting from deposition of A4 or beta-peptide A4[1-42]. They are most numerous in limbic cortex & association cortex. * see figure Classification: Two types of plaques have been described. 1) neuritic plaques (10 to > 120 um in diameter) a) amyloid core (thioflavin & Congo-red positive) b) dystrophic neurites 1] occur both within & immediately surrounding amyloid deposits 2] often dilated & tortuous 3] marked ultrastructural abnormalities a] enlarged lysosomes b] numerous mitochondria c) paired helical filaments c) activated microglia d) reactive astrocytes 1] often ring the outside of the plaque 2] processes may extend toward central amyloid core e) local inflammatory response 1] acute-phase proteins 2] cytokines 3] complement components 4] proteases 2) diffuse plaques a) diffuse deposits of amyloid 1] A4/42 is 1st component to appear in amyloid deposits 2] A4/40 precipitates on pre-existing A4/42 deposits b) no dystrophic neurites c) no associated reactive microglia d) no inflammatory response e) observed in association & limbic cortex, cerebellum, thalamus & striatum f) may NOT stain with thioflavin & Congo-red stains g) may be immature amyloid plaques h) may be envisioned as dynamic structures with active A4 deposition & dissolution Epidemiology: - air pollution associated with increased risk [13] Components: 1) inorganic aluminosilicate* 2) A4 or beta-protein* a) diffuse plaques contain A4/42 alone b) neuritic plaques contain both A4/40 & A4/42 c) amino terminal truncated forms of A4/42 (3-42, 4-42, 5-42, 8-42 & 9-42) identified as major constituents [8] 3) alpha-1 antichymotrypsin 4) amyloid P component 5) apolipoprotein E 6) ICAM-1 7) non A-beta component of AD amyloid 8) butyrylcholinesterase 9) diffuse amyloid deposits may contain GM1 ganglioside [7] * the core of senile plaques has two major components, inorganic aluminosilicate & A4 or beta-protein. Formation: 1) may be formed by lysis of neurons & astrocytes containing A4/42 [10,11] 2) neuritic plaques thought to develop over months to years [6] 3) plaques may form (& be cleared) rapidly in a mouse model [12] Inhibitors of ACAT1 enhance beta peptide & amyloid plaque removal in a mouse model for Alzheimer's disease [9] Laboratory: - amyloid in brain by light microscopy Radiology: -

General

abnormal morphologic structure (malformation)

Properties

PATHOLOGY: aging Alzheimer's disease

References

  1. Schubert et al Science 241:223 1988
  2. Marx Science 243:1664 1989 (alpha-1 antichymotrypsin)
  3. UI90304597 (amyloid P component)
  4. Verbeek MM et al Accumulation of intercellular adhesion molecule-1 in senile plaques in brain tissue of patients with Alzheimer's disease. Am J Pathol. 1994 Jan;144(1):104-16. PMID: 7904796
  5. Role of cholinergic therapy in treatment of Alzheimer's disease & other dementias, Farlow, M et al, 2001
  6. Selkoe DJ. Alzheimer's disease: genes, proteins, and therapy. Physiol Rev. 2001 Apr;81(2):741-66. Review. PMID: 11274343
  7. Michikawa et al J Neurosci 21:7226, 2001
  8. Sergeant N et al, Truncated beta-amyloid peptide species in pre-clinical Alzheimer's disease as new targets for the vaccination approach. J Neurochem. 2003 Jun;85(6):1581-91. PMID: 12787077
  9. Tanzi RE. In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004 (reference to Oct 2004 issue of Neuron
  10. Nagele RG, D'Andrea MR, Lee H, Venkataraman V, Wang HY. Astrocytes accumulate A beta 42 and give rise to astrocytic amyloid plaques in Alzheimer disease brains. Brain Res. 2003 May 9;971(2):197-209. PMID: 12706236
  11. D'Andrea MR, Nagele RG, Wang HY, Lee DH. Consistent immunohistochemical detection of intracellular beta-amyloid42 in pyramidal neurons of Alzheimer's disease entorhinal cortex. Neurosci Lett. 2002 Nov 29;333(3):163-6. PMID: 1242937
  12. Meyer-Luehmann M et al, Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer's disease. Nature 2008, 451:720 PMID: 18256671
  13. Iaccarino L, La Joie R, Lesman-Segev OH et al Association Between Ambient Air Pollution and Amyloid Positron Emission Tomography Positivity in Older Adults With Cognitive Impairment. JAMA Neurol. Published online November 30, 2020. PMID: 33252608 https://jamanetwork.com/journals/jamaneurology/article-abstract/2773645

Databases & Images

OMIM 269800 images related to amyloid plaque