Tabular neuropathology data
This section provides an overview of the neuropathology data available on the Laboratory of Neuroimaging Image and Data Archive (LONI IDA) website. The neuropathology data includes the following:
Neuropathology Results – Includes postmortem neuropathologic, gross, and microscopic findings for research for ADNI participants using the NACC (National Alzheimer’s Coordinating Center) form data (v10/v11)
Neuropathology Images – Includes digitized Whole Slide Images (WSI) of stained brain tissue slides made available from ADNI brain donations
Introduction to Neuropathology in ADNI
The ADNI Neuropathology Core (NPC) was established in 2007 during ADNI1 to help the participating sites across the United States and Canada offer brain donation to the ADNI participants. Neuropathologic examination is essential to validate the clinical diagnoses in the ADNI study groups. The findings thus far show that the ADNI cohort includes multiple, additional neurodegenerative pathologies besides AD. These non-AD pathologies often accompany or impersonate AD. An assessment of postmortem brain tissue can provide definitive neuropathologic explanations for clinical changes and provide perspective on the variability of individual features along the complex clinicopathologic spectrum of dementia.
The neuropathology data in ADNI are derived from application of the National Institute on Aging-Alzheimer’s Association guidelines for the neuropathologic assessment of AD. Neuropathology data may be considered the ‘gold standard’ against which other clinical, neuropsychological, genetic, neuroimaging, and body fluid biomarkers may be compared. Neuropathology data may be used to underpin multimodal studies of the natural history of AD. Data relevant to other neurodegenerative diseases are derived from the application of other appropriate contemporary neuropathologic guidelines.
In addition to offering neuropathology data, the ADNI NPC will provides digitized histology slides from new and archived cases during ADNI4.
ADNI Neuropathology Core
The ADNI Neuropathology Core is led by Richard Perrin, MD, PhD at Washington University in St. Louis, Missouri. At Washington University, he directs the Translational Human Neurodegenerative Disease Research (THuNDR) Laboratory, where many collaborative translational research projects are supported to focus on the understanding and development of biomarkers and treatments for neurodegenerative diseases.
More information about the THuNDR Lab can be found here.
Data organization
The tabular Neuropathology Results data can be found under the ‘Neuropathology’ tab of the study files interface on the IDA and is divided into two sections:
1. NACC Neuropathology Data Form
2. NACC Neuropathology Data Methods (PDF)
The Neuropathology Images can be found under the Simple Image Search interface on the IDA.
To search for the Neuropathology Images, change the Modality under IMAGE INFORMATION to ‘Path’.
To view all of the digital brain tissue slides available, change the Image Count to ‘ALL’. The image count defaults to 500, which will only preview a portion of the digital slides available.
Brain tissue collection and processing
Brain tissue is collected at autopsy from individuals who have passed away, with consent obtained prior to death or by next of kin after death. The brain is bisected into cerebral hemispheres and brainstem by a midline/sagittal cut. The right cerebral hemisphere is frozen, and the left hemisphere is placed in a fixative of 10% neutral buffered formalin.
For sites that retain tissue for their own assessment, a standard set of formalin-fixed paraffin-embedded brain tissue blocks, and frozen tissue slabs are forwarded to the ADNI Neuropathology Core at Washington University in St. Louis, Missouri.
Brain Tissue Regions Sampled for the ADNI Neuropathology Protocol include:
Middle frontal gyrus
Superior and middle temporal gyri
Inferior parietal lobe (angular gyrus)
Occipital lobe to include the calcarine sulcus and parastriate cortex
Anterior cingulate gyrus at the level of the genu of the corpus callosum
Precentral gyrus
Posterior cingulate gyrus and precuneus at the level of the splenium
Amygdala and entorhinal cortex
Hippocampus and parahippocampal gyrus at the level of the lateral geniculate nucleus
Striatum (caudate nucleus and putamen) with olfactory cortex at the level of the nucleus accumbens
Striatum and pallidum at the level of the anterior commissure to include nucleus basalis of Meynert, basal forebrain, and septum
Thalamus and subthalamic nucleus
Midbrain with red nucleus
Pons with locus coeruleus
Medulla oblongata
Cerebellum with dentate nucleus
Spinal cord
Once brain tissue is recieved, the following processing steps are carried out:
| Slicing and Photographing | Before the brain tissue is cut or sliced further, photographs are taken for gross examination. Photographs are taken again at different intervals of processing the brain tissue. |
| Tissue Blocking | The fixed tissue is then dissected into smaller blocks that represent specific brain areas. |
| Tissue Embedding | After the fixed brain tissue is blocked, the tissue is placed into cassettes, undergoes tissue processing (automated process of dehydrating, clearing, and infiltrating tissues with embedding media), and embedded in paraffin wax. |
| Tissue Sectioning | The tissue is then sectioned into thin slices (~6 μm) using a microtome and then mounted onto glass slides. |
| Tissue Staining | For most cases we will prepare and examine 5 sets of histology slides (stained with H&E and with IHC using anti-beta-amyloid [10D5, Eli Lilly], anti-phosphorylated tau [PHF1, Feinstein Institute for Medical Research, Manhasset, NY 10461], anti-a-synuclein [LB509, MilliiporeSigma], and anti-phosphorylated TDP-43 [pTDP-43, Cosmo Bio USA] antibodies). |
Assessment of pathology
Pathological lesions within the brain are assessed using established neuropathologic diagnostic criteria. The NIA-AA criteria recognize that AD neuropathologic change (ADNC) may occur in the apparent absence of cognitive impairment. In accordance with the NIA-AA protocol, an “ABC” score for ADNC is generated from histopathologic assessments of the anatomic distribution of amyloid β plaques (A), the distribution and density (staging) of neurofibrillary tangles (B), and the maximal density of neocortical neuritic plaques (C). In addition, detailed methods for assessing common co-morbid conditions such as Lewy body disease, vascular pathology and associated brain injury, hippocampal sclerosis, argyrophilic grain disease, and TAR DNA binding protein (TDP) immunoreactive inclusions are included.
Neuropathology data are captured in the format of the Neuropathology Data Form Version 10 or form 11 of the National Alzheimer’s Coordinating Center (NACC) established by the National Institute on Aging/NIH (U01 AG016976). The Neuropathology NACC Form Version 11 includes specific questions/prompts to gather information about aging-related tau astrogliopathy (ARTAG). For ADNI cases with information gathered using Neuropathology NACC Form Version 10, the presence of ARTAG is indicated under “OTHER PATHOLOGIC DIAGNOSES.” For more information see:
Neuropathology NACC Form Version 10
Neuropathology Coding Guidebook NACC Version 10: NACC Home | National Alzheimer’s Coordinating Center
Neuropathology Data Collection Form NACC Version 10: NACC Home | National Alzheimer’s Coordinating Center
Neuropathology Data Dictionary NACC Version 10: NACC Home | National Alzheimer’s Coordinating Center
Neuropathology NACC Form Version 11
Neuropathology Coding Guidebook NACC Version 11: https://files.alz.washington.edu/documentation/np11-guidebook.pdf
Neuropathology Data Collection Form NACC Version 11: https://files.alz.washington.edu/documentation/np11-form.pdf
Neuropathology Data Dictionary NACC Version 11: https://files.alz.washington.edu/documentation/np11-ded.pdf
Brain Tissue Slide Digitization Process
The slide sets are scanned using the Leica Aperio AT2 digital slide scanner to produce high-resolution digital images. First, the glass slides are cleaned using isopropyl alcohol and a lint-free wipe to remove any unwanted particles for optimum image quality. Then, the glass slides are loaded into the Autoloader of the AT2. Specific parameters are set prior to starting the scanning process. A ‘snapshot’ is captured of each slide to verify calibration point, set magnification, set scan area, and set focus points. Then, a high-resolution image is captured, at 20X magnification, for each slide to produce a Whole Slide Image (WSI).
Note that this document does not address the storage, formatting, or any other aspect of working with Whole Slide Images themselves, which are available in .TIFF format.