Modular and laminar pathology of Brodmann’s area 37 in Alzheimer’s disease

Abstract

Previous studies suggested a relationship between severity of symptoms and the degree of neurofibrillary tangles (NFTs) clustering in different areas of the cortex in Alzheimer's disease (Lee et al.). The posterior inferior temporal cortex or Brodmann's area (BA37) is involved in object naming and recognition memory. But the cellular architecture and connectivity and the NTF pathology of this cortex in AD received inadequate attention. In this report, we describe the laminar distribution and topography of NFT pathology of BA 37 in brains of AD patients by using thionin staining for Nissl substance, thioflavin-S staining for Neurofibrillary tangles (NFTs), and phosphorylated tau (AT8) immunohistochemistry. NFTs mostly occurred in cortical layers II, III, V and VI in the area 37 of AD brain. Moreover, NFTs appeared like a patch or in cluster pattern along the cortical layers III and V and within the columns of pyramidal cell layers. The abnormal, intensely labeled AT8 immunoreactive cells were clustered mainly in layers III and V. Based on previously published clinical correlations between cognitive abnormalities in AD and the patterns of laminar distributed NFT cluster pathology in other areas of the brain, we conclude that a similar NFT pathology that severely affected BA 37, may indicate disruption of some forms of naming and object recognition related circuits in AD. KeywordsNeurofibrillary tangles; posterior inferior temporal cortex; Brodmann's area 37; phosphorylated tau; laminar distribution; memory impairment; object recognition 6 Address correspondence to: Asgar Zaheer, Department of Neurology, The University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, Tel. 319-335-8529; Fax 319-335-8528, E-Mail: asgar-zaheer@uiowa.edu, Or Ramasamy Thangavel, Department of Neurology, The University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, Tel. 319-335-8520; Fax 319-335-8528, E-Mail: ramasamythangavel@uiowa.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Neurons in the cerebral cortex are organized horizontally into lamina and vertically into columns and modules. These organized neurons, with similar response properties, form fundamental anatomical and physiological units of the cortex (Fujita et al., 1992, Saleem et al., 1993, Tanigawa et al., 1998. NIH Public AccessIn Alzheimer's disease, the characteristic neuropathological lesions of neurofibrillary tangles (NFTs) exhibit a specific laminar and regional distribution in different areas of brain. (Hof and Morrison, 1990, Hof et al., 1992, Hof, 1997. The modular/columnar organized NFT pathology of the h...

Cortical laminar tau deposits and activated astrocytes in Alzheimer’s disease visualised by 3H-THK5117 and 3H-deprenyl autoradiography

“…In 2008, Thangavel et al . described the pathology in the fusiform gyrus (BA37)32 and the posterior parahippocampal gyrus33 in detail. In the fusiform gyrus, the NFTs appear in a peculiar pattern and are distributed in the pyramidal cells of layers III and V. Although all the AD cases in our study were in late Braak tau stages, the laminar profiles for both tau and activated astrocytes were similar within but different across cases.…”

The Abnormally Phosphorylated Tau Lesion of Early Alzheimer’s Disease

“…The sections were processed for immunohistochemistry as previously described [22,25]. Nearly adjacent sections for each case were immunolabeled using an avidin-biotin peroxidase complex procedure by using AT8 antibody.…”

Pathological Stages of Abnormally Processed Tau Protein During Its Aggregation into Fibrillary Structures in Alzheimer’s Disease

“…These particular changes in the tau molecule also occur in the temporal cortex. It has been reported that NFTs in this area display a laminar distribution occurring mostly in cortical layers II,III,V, and VI (Thangavel et al, 2008). These structures are also conformed of tau protein phosphorylated at several domains (Thangavel et al, 2008;Guillozet-Bongaarts et al, 2006) and some showing immunoreactivity to Alz-50 antibody (de la Monte et al, 1992).…”

“…It has been reported that NFTs in this area display a laminar distribution occurring mostly in cortical layers II,III,V, and VI (Thangavel et al, 2008). These structures are also conformed of tau protein phosphorylated at several domains (Thangavel et al, 2008;Guillozet-Bongaarts et al, 2006) and some showing immunoreactivity to Alz-50 antibody (de la Monte et al, 1992). Summarizing, during the progression of early and intermediate stages of AD, the discriminatory presence of each conformational event sets the dynamic behavior of tau during the maturation of NFTs, started by the N-terminus folding that is caused by the phosphorylation of specific domains.…”

“…These data clearly show the unsynchronized, by time, processing of NFTs in the hippocampus and the late time processing of NFTs in the ERC-II area, emphasizing that this is the more vulnerable area for the onset of the AD neurofibrillary pathology. Regarding isocortical areas, which are the later affected regions in AD progression, most of the changes in tau protein that are seen in the NFTs, mostly correspond to increased phosphorylation (Thangavel et al, 2008). However along the progression of the disease, truncation of tau protein at Asp 421 also has www.intechopen.com Pathological Stages of Abnormally Processed Tau Protein During Its Aggregation into Fibrillary Structures in Alzheimer's Disease 147 been described in some of NFTs proliferating in the temporal isocortex (Guillozet-Bongaarts et al, 2006).…”