Feasibility Study: Comparison of Frontal Cortex Needle Core Versus Open Biopsy for Detection of Characteristic Proteinopathies of Neurodegenerative Diseases

Abstract

The clinical diagnosis and classification of neurodegenerative diseases based on clinical examination or available biomarkers are currently insufficiently accurate. Although histological examination is considered the gold standard for diagnosis, brain biopsies have been avoided because of the high risk-benefit ratio. However, brain biopsies have previously been performed with a craniotomy and excision of approximately 1 cc of cerebral cortex tissue, and it is possible that needle core brain biopsies would have a lower morbidity and mortality risk. Here, we compared the ability of simulated needle core biopsy versus simulated open biopsy to detect the frontal cortex histopathology associated with common neurodegenerative diseases in the elderly using 144 autopsy-proven cases. Simulated needle core biopsy, as compared to simulated open biopsy, gave close to 90% sensitivity and specificity for identifying graded densities of β-amyloid and neuritic plaques, neurofibrillary tangles, phosphorylated α-synuclein, and phosphorylated TDP-43 pathology. This study shows that the presence and densities of the most common molecular pathologies may be histopathologically assessed in simulated frontal cortex needle biopsies with accuracy very close to that obtained by open cortical biopsy. An accurate estimation of the morbidity and mortality risk associated with cortical needle core biopsy will require specifically designed clinical trials in appropriate subjects.

Severe hyposmia distinguishes neuropathologically confirmed dementia with Lewy bodies from Alzheimer’s disease dementia

“…Biofluids and PET imaging approaches have so far been unsuccessful in providing the required accuracy for identifying LBD [113][114][115]. Simulation studies have suggested that cortical biopsy [116][117][118][119] would have high sensitivity and specificity for DLB, and usage of needle cores rather than open biopsy may reduce morbidity to acceptable levels [116]. Biopsy of the peripheral nervous system [120], particularly the submandibular gland [121][122][123][124], also shows promise for diagnosing DLB.…”

Severe Hyposmia Distinguishes Neuropathologically Confirmed Dementia with Lewy Bodies from Alzheimer’s Disease Dementia

“…Biofluids and PET imaging approaches have so far been unsuccessful in providing the required accuracy for identifying LBD [112][113][114]. Simulation studies have suggested that cortical biopsy [115][116][117][118] would have high sensitivity and specificity for DLB, and usage of needle cores rather than open biopsy may reduce morbidity to acceptable levels [115]. Biopsy of the peripheral nervous system [119], particularly the submandibular gland [120][121][122], also shows promise for diagnosing DLB.…”

Faster Cognitive Decline in Dementia due to Alzheimer Disease with Clinically Undiagnosed Lewy Body Disease

“…Biofluids and PET imaging approaches have so far been unsuccessful in providing the required accuracy for identifying LBD [87][88][89]. Simulation studies have suggested that cortical biopsy [90][91][92][93] would have high sensitivity and specificity for DLB, and usage of needle cores rather than open biopsy may reduce morbidity to acceptable levels [90] but would not detect AD-LB subjects as they mostly lack cortical LB pathology. Biopsy of the peripheral nervous system [94], particularly the submandibular gland [86;95-97], shows Faster Decline with Unsuspected Lewy Bodies promise for diagnosing DLB but peripheral LBD pathology is relatively rare in AD-LB.…”