Journal: Alzheimer's & Dementia

Article Title: The Alzheimer's Disease Neuroimaging Initiative Neuropathology Core: An update

doi: 10.1002/alz.14253

Figure Lengend Snippet: Schematic of standardized ADNI NPC histologic sampling. After fresh sagittal bisection, freezing of the right hemibrain, and thorough formalin fixation of the left hemibrain, the left hemibrain is sliced (supratentorial structures, coronally; cerebellum, sagittally; brainstem and associated cervical spinal cord, axially), and at least 16 regions are sampled, with cervical spinal cord included as a 17th region, when available. Other areas are sampled as needed to enable histological examination of any macroscopic abnormalities outside the standard areas. Each histologic sample is processed into paraffin wax and 6‐µm glass‐mounted sections of each are subsequently stained with H&E and by IHC for beta‐amyloid, phosphorylated tau, alpha‐synuclein, and pTDP‐43 as described in Methods (Section ). Areas sampled: 1: middle frontal gyrus; 2: anterior cingulate gyrus; 3: striatum with nucleus accumbens and olfactory cortex; 4: precentral gyrus; 5: pallidum and basal forebrain with nucleus basalis of Meynert; 6: superior and middle temporal gyri; 7: amygdala with ambient, fusiform and inferior temporal gyri; 8: thalamus with subthalamic nucleus; 9: hippocampus with parahippocampal gyrus, fusiform gyrus, inferior temporal gyrus; 10: posterior cingulate gyrus and precuneus; 11: angular gyrus (parietal lobe); 12: calcarine sulcus and parastriate cortex; 13: dorsal cerebellar cortex with dentate nucleus; 14: midbrain with red nucleus; 15: pons with locus coeruleus; 16: medulla with dorsal motor nuclei and inferior olive; 17: cervical spinal cord (when available). ADNI, Alzheimer's Disease Neuroimaging Initiative; H&E, hematoxylin and eosin; IHC, immunohistochemistry; NPC, Neuropathology Core.

Article Snippet: From each of 17 formalin‐fixed, paraffin‐embedded (FFPE) tissue samples per case (Figure ), the ADNI NPC stains glass slide‐mounted 6‐µm‐thick sections with hematoxylin and eosin (H&E) and by standard (3,3′‐diaminobenzidine [DAB]) IHC using a Leica Bond III autostainer and antibodies for Aβ (10D5, Eli Lilly, Indianapolis, IN, USA); phosphorylated tau (mouse monoclonal PHF‐1, Feinstein Institute for Medical Research, Manhasset, NY, USA); phosphorylated alpha‐synuclein (rabbit monoclonal, Catalog No. CG1656, Cell Applications, San Diego, CA, USA) or non‐phosphorylated alpha‐synuclein (mouse monoclonal LB509, MilliporeSigma Burlington, MA, USA); and phosphorylated TAR DNA binding protein 43 (pTDP‐43) (mouse monoclonal pTDP‐43 [pS409/410], Cosmo Bio USA, Carlsbad, CA, USA).

Techniques: Sampling, Paraffin Wax, Staining, Immunohistochemistry

Journal: Alzheimer's & Dementia

Article Title: The Alzheimer's Disease Neuroimaging Initiative Neuropathology Core: An update

doi: 10.1002/alz.14253

Figure Lengend Snippet: ADNI participant diagnosed clinically with moderate ADD and mild cerebrovascular disease (continued from Figure ). The 12‐panel array on the left illustrates the distribution of Lewy bodies and Lewy neurites immunoreactive for phosphorylated alpha‐synuclein, most consistent with the limbic (transitional) stage ²² , ²³ and Braak stage 3 or 4, likely to contribute to impaired cognition, but generally inconsistent with symptomatic idiopathic Parkinson's disease. The upper right panel illustrates an H&E‐stained microinfarct identified by chance within the precentral gyrus; as a presumptive representative of other similar undetected neocortical microinfarcts, even an isolated lesion such as this has been shown to correlate with additive cognitive impairment. ¹⁹ The lower right panels illustrate the severe, widespread CAA in this case, even affecting capillaries within the precentral gyrus, and its regionally severe arteriolosclerosis; either of these vasculopathic processes, or both, may have increased the likelihood of cortical microinfarction. ACG, anterior cingulate gyrus; ADD, AD dementia; ADNI, Alzheimer's Disease Neuroimaging Initiative; Amy, amygdala; CAA, cerebral amyloid(‐beta) angiopathy; H&E, hematoxylin and eosin; Med, medulla oblongata; IPL, inferior parietal lobule; LC, locus coeruleus; MFG, middle frontal gyrus; Motor Ctx, primary motor cortex (precentral gyrus); NBM, nucleus basalis of Meynert; Olf bulb, olfactory bulb; Olf ctx, olfactory cortex; TransEntCtx, transentorhinal cortex; SNpc, substantia nigra pars compacta; STG, superior temporal gyrus.

Article Snippet: From each of 17 formalin‐fixed, paraffin‐embedded (FFPE) tissue samples per case (Figure ), the ADNI NPC stains glass slide‐mounted 6‐µm‐thick sections with hematoxylin and eosin (H&E) and by standard (3,3′‐diaminobenzidine [DAB]) IHC using a Leica Bond III autostainer and antibodies for Aβ (10D5, Eli Lilly, Indianapolis, IN, USA); phosphorylated tau (mouse monoclonal PHF‐1, Feinstein Institute for Medical Research, Manhasset, NY, USA); phosphorylated alpha‐synuclein (rabbit monoclonal, Catalog No. CG1656, Cell Applications, San Diego, CA, USA) or non‐phosphorylated alpha‐synuclein (mouse monoclonal LB509, MilliporeSigma Burlington, MA, USA); and phosphorylated TAR DNA binding protein 43 (pTDP‐43) (mouse monoclonal pTDP‐43 [pS409/410], Cosmo Bio USA, Carlsbad, CA, USA).

Techniques: Staining, Isolation