Neuropathology Evaluation

The neuropathological phenotyping of banked specimens follows a predefined decision-tree algorithm. This decision tree incorporates limited screening vs. full evaluation depending on the age of the donor and phenotype. The limited screen approach is intended for young individuals (those under age 45) who present with no phenotypic evidence that can be associated with neuropathology. The intent of this approach is to maximize the availability of tissue specimens for research. The full evaluation arm is intended for those cases that are elderly and/or present with suspected neuropathology (e.g., Alzheimer’s disease, Parkinson’s disease, stroke).

All neuropathology evaluations are made by a board certified Icahn School of Medicine at Mount Sinai neuropathologist.

  • After excision and documentation of gross features, the brain is immediately cooled on ice.
  • The specimen is photographed, weighed, and divided mid-sagittally.
  • The right half of the brain, and any regions from the left brain containing gross lesions, are fixed by suspension immersion in cold (4oC) freshly prepared 4 percent buffered paraformaldehyde for neuropathological evaluation and neuroanatomical studies.
  • The left half is sectioned in the coronal plane into 8 mm slabs and snap frozen in liquid nitrogen cooled isopentane, vacuum heat-sealed in thick-walled pouches, and stored in one of 30 alarmed ultra-low freezers.
  • On completion of neuropathological and clinical diagnosis procedures (generally within 60 days of autopsy), tissues are considered available for distribution to research laboratories.
  • In general the following regions are used for histological examination: Superior and middle frontal gyrus, orbital cortex, watershed territories (Brodmann areas 4,3,1,2), basal ganglia with basal forebrain, amygdala, hippocampus (rostral and caudal levels with adjacent amygdala, parahippocampal and inferior temporal cortex), superior temporal gyrus, parietal cortex (angular gyrus), calcarine cortex, hypothalamus with mammillary bodies, thalamus, midbrain, pons, medullar, cerebellar vermis, and lateral cerebellar hemisphere.
  • Sections from paraffin embedded blocks are stained using any or all of the following methods/stains: hematoxylin and eosin, modified Bielschowsky, modified thioflavin S, anti-amyloid, anti-abnormally phosphorylated tau, anti-TDP-43, anti-ubiquitin and -synuclein.
  • Cerebrovascular pathology is assessed using an adaptation of the protocols described by Vinters et al.(2000); congophilic angiopathy is rated using the criteria developed by Vonsattel, et al.(1991). Ischemic lesions are tabulated and mapped as: cystic infarcts (i.e., greater than 1 cm in greatest dimension); lacunar infarcts (i.e., less than 1 cm in greatest dimension); microinfarcts (ischemic lesions noted only on microscopic examination). The hippocampus is evaluated separately for sclerosis (focal areas of neuronal loss with prominent gliosis in the absence of prominent localized ghost tangle formation).
  • Diagnosis of Alzheimer’s disease and other dementing neuropathologies are based on CERAD(1991), Khatchaturian(1985), NIA-Reagan Institute Consensus recommendations(1997) and the NIA-Alz-Assoc. criteria(2012). Criteria and sampling procedures developed by Dickson et al.(2009) and staging by Braak et al. (2002) are used for the diagnosis of Parkinson’s disease. The methods for the description of cerebrovascular pathologies are listed above. Unaffected cases are defined as those who do not meet diagnostic criteria for any discernible neuropathologic condition, although all incidental findings and all sub-threshold lesion density measures are retained and are available to investigators.

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James J Peters VA Medical Center
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