anatomic predilection of Alzheimer's pathology
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Pathology
- evolving lesional pattern in AD reflects evolution of the cerebral cortex
- highest densities & earliest lesions occur in the anterior mesocortical transitional zone between allocortex & neocortex
- from there, involvement extends into the hippocampus & neocortex[5]
Neurofibrillary lesions* occur prior to beta-amyloid lesions in most patients with AD[9]
Predilection of neurofibrillary lesions*
- locus ceruleus may be earliest affected
- abnormal tau aggregates (pretangles) develop within proximal axons of noradrenergic locus coeruleus projection neurons in the absence of tau lesions (pretangles, NFTs) in the entorhinal cortex or beta-amyloid pathology in the neocortex
- AD may begin in the locus ceruleus & progress to the entorhinal cortex via trans-synaptic transport of tau protein aggregates & neuron-to-neuron transmission
- a prion-like mechanism is suggested[9]
- hippocampus
- entorhinal cortex
- stellate neurons in layer 2 (affected very early)
- deposits of tau protein in the entorhinal cortex may be identified in people age >= 30 years destined to suffer from late-onset AD[10]
- CA1 pyramidal cells affected later than entorhinal cortex
- subiculum
- entorhinal cortex
- association cortex
- frontal cortex
- temporal cortex
- parietal cortex
- clustering of neurofibrillary pathology in layers 3 & 5 of the association cortex[8] (see isocortex)
- selectively vulnerable regions may be associated with neural plasticity[8]
- nucleus basalis
- neurofibrillary tangles occur as a very early event[4]
- olfactory system
- olfactory bulb & tract effected as early as entorhinal cortex[6]
- olfactory bulb & nerve involvement begins in Braak stage 2[7]
- also see olfaction & Alzheimer's disease
- raphe nuclei
* neuropil threads & neurofibrillary tangles, see Braak staging
- microglial activation & PHF-tau propagate jointly across Braak stages[12]
Predilection of beta-amyloid lesions
- earliest lesions occur in the basal temporal neocortex[9]
- from there, beta-amyloid pathology enters the entorhinal cortex & hippocampal formation
- primary neocortex is affected last
Areas relatively spared:
distribution of amyloid pathology in AD differs from that of traumatic brain injury[11]
- based upon histopathology of neurofibrillary tangles & neuropil threads in autopsy specimens[3]
- distribution & packing density of amyloid plaques varies widely & is of little significance for differentiation of early neuropathologic stages.[3]
- intraneuronal lesions are confined to a small number of neuronal types
- most of these neurons mature late during ontogenesis
- projection neurons with a disproportionately long in relation to cell body size & sparsely myelinated axon are especially prone to the AD pathology[9]
More general terms
Additional terms
- Braak staging of Alzheimer's disease
- entorhinal cortex (Brodmann's area 28)
- hippocampus (hippocampal formation)
- subiculum
References
- ↑ Greenfield's Neuropathology, 5th ed., 1992
- ↑ Arendt T. Neurodegeneration and plasticity. Int J Dev Neurosci. 2004 Nov;22(7):507-14. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15465280
- ↑ 3.0 3.1 3.2 Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol (Berl). 1991;82(4):239-59. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1759558
- ↑ 4.0 4.1 Mesulam M, Shaw P, Mash D, Weintraub S. Cholinergic nucleus basalis tauopathy emerges early in the aging-MCI-AD continuum. Ann Neurol. 2004 Jun;55(6):815-28. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15174015
- ↑ 5.0 5.1 Braak H, Rub U, Schultz C, Del Tredici K. Vulnerability of cortical neurons to Alzheimer's and Parkinson's diseases. J Alzheimers Dis. 2006;9(3 Suppl):35-44. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16914843
- ↑ 6.0 6.1 Christen-Zaech S, Kraftsik R, Pillevuit O, Kiraly M, Martins R, Khalili K, Miklossy J. Early olfactory involvement in Alzheimer's disease. Can J Neurol Sci. 2003 Feb;30(1):20-5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/12619779
- ↑ 7.0 7.1 Attems J and Jellinger KA, Olfactory tau pathology in Alzheimer disease and mild cognitive impairment. Clin Neuropathol. 2006, 25:265 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17140156
- ↑ 8.0 8.1 8.2 Esiri MM and Chance SA Vulnerability of Alzheimer's pathology in the neocortex: the roles of plasticity and columnar organization. J Alzheimer's disease 2006, 9(3 Suppl):79 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16914847
- ↑ 9.0 9.1 9.2 9.3 9.4 Braak H and Tredici KD Alzheimer's pathogenesis: is there neuron-to-neuron propagation? Acta Neuropathol (2011) 121:589-595 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21516512
- ↑ 10.0 10.1 Kunz L et al. Reduced grid-cell-like representations in adults at genetic risk for Alzheimer's disease. Science 2015 Oct 23; 350:430. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26494756
- ↑ 11.0 11.1 Anderson P Amyloid Pattern in TBI Different Than in Alzheimer's Medscaope. February 05, 2016 http://www.medscape.com/viewarticle/858463
- ↑ 12.0 12.1 Pascoal TA, Benedet AL, Ashton NJ et al. Microglial activation and tau propagate jointly across Braak stages. Nat Med 2021. August 21 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34446931 https://www.nature.com/articles/s41591-021-01456-w