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Cited by 578Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Laminar and regional distributions of neurofibrillary tangles and neuritic plaques in Alzheimer’s disease: a quantitative study of visual and auditory cortices

Open access
Lewis, DA, Campbell, MJ, Terry, RD, Morrison, JH·1987·The Journal of Neuroscience
DOI 10.1523/jneurosci.07-06-01799.1987PMC PMC6568896
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Abstract

The number of Thioflavine S-positive neurofibrillary tangles (NFT) and neuritic plaques (NP) was determined in visual and auditory cortical regions of 8 patients with Alzheimer's disease. On both a regional and laminar basis, NFT exhibited very distinctive and consistent distribution patterns. The mean (+/- SEM) number of NFT in a 250-micron- wide cortical traverse was very low in area 17, primary visual cortex (0.9 +/- 1.0), increased 20-fold in the immediately adjacent visual association cortex of area 18 (19.7 +/- 3.6), and showed a further doubling in area 20, the higher-order visual association cortex of the inferior temporal gyrus (35.5 +/- 8.8). Similar differences in NFT number were present between primary auditory (1.6 +/- 0.5) and auditory association (18.9 +/- 5.4) regions. On a laminar basis, NFT were predominantly present in layers III and V, although there were striking regional differences in the proportion of NFT in these 2 layers. Layer III contained 79% of the NFT in layers III and V in area 18, 41% in area 20, and only 27% in area 22. In contrast, NP showed different, and less specific, regional and laminar distribution patterns. Total NP number was similar in the 3 visual areas, although there were marked regional differences in the type of NP present. Nearly 80% of the NP in area 17 was of the NPc type (i.e., contained a dense, brightly fluorescent core), whereas over 70% of the NP in both areas 18 and 21 was of the NPnc type (i.e., lacked a dense, brightly fluorescent core). NP were present in every cortical layer but were most numerous in layers III and IV. The distinctive distribution patterns of NFT are very similar to the regional and laminar locations of long corticocortical projection neurons in homologous regions of monkey neocortex. This association suggests that NFT reside in the cell bodies of a subpopulation of pyramidal neurons, namely, those that furnish long corticocortical projections. In contrast, the distribution patterns of NP suggest that multiple neuronal systems contribute to their formation.

AI snapshot

Written from the paper’s full text.

TL;DR

In 8 Alzheimer’s disease brains, neurofibrillary tangles (NFT) increased from primary to association visual and auditory cortices and concentrated in layers III and V, whereas neuritic plaques (NP) were more evenly distributed across visual areas and layers. The NFT pattern resembled the distribution of long corticocortical projection neurons, suggesting selective vulnerability of those pyramidal neurons, while NP likely have multiple origins.

Key findings

  • NFT counts per 250-µm-wide cortical traverse were 0.9 ± 1.0 in area 17, 19.7 ± 3.6 in area 18 (~20-fold increase), and 35.5 ± 8.8 in area 20 (further doubling); auditory regions showed 1.6 ± 0.5 in area 41 versus 18.9 ± 5.4 in area 22 (>10-fold increase).
  • NFT were predominantly in layers III and V; layer III contained 79% of NFT in layers III and V in area 18, 41% in area 20, and 27% in area 22.
  • Total NP number was similar across visual areas: 17.9 ± 2.2 in area 17, 18.2 ± 1.9 in area 18, and 21.3 ± 0.9 in area 20. NP type differed regionally: 79% of NP in area 17 were NPc, whereas 72% in area 18 and 76% in area 20 were NPnc.
  • NFT number was inversely correlated with age in areas 17 (r = −0.809, p = 0.051), 18 (r = −0.941, p = 0.005), 20 (r = −0.801, p = 0.056), and 41 (r = −0.868, p = 0.056), but not area 22; NP number and type were not significantly associated with age.

Methods

  • Brains from 8 patients with clinically diagnosed AD (age range 48–82 years), confirmed neuropathologically, were sampled from medial occipital lobe, inferior temporal gyrus, and Heschl’s gyri/adjacent superior temporal gyrus; sections were stained with Thioflavine S and cresyl violet.
  • NFT were counted in a 250-µm-wide cortical traverse from 10 sections per brain at 250×; NP were counted in a 500-µm-wide traverse from 8 sections per brain at 100× in the 3 visual areas and classified as NPc or NPnc.
  • Laminar distributions were determined by comparing distances from the pial surface to adjacent Nissl-stained boundaries; differences were tested with 2-factor repeated-measures ANOVA, Tukey comparisons, and Pearson correlations.

Limitations

  • Stated: layer V pyramidal neurons also give rise to corticofugal fibers, so NFT could develop in layer V neurons that do not furnish long corticocortical projections; some NPc may have been misclassified as NPnc because 40-µm sections can cut peripheral portions of plaques; other cortical neurons may also develop NFT.
  • Evident: the sample was small (8 patients, with some regional analyses using 5 or 6 cases), and the link to long corticocortical projection neurons relies on comparison with monkey anatomical data rather than direct human tracing.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1523/jneurosci.07-06-01799.1987

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 73 cited sources checked · 0 supported · 0 flagged

  • Findingown data
    § Laminar and Regional Distributions of Neurofibrillary Tangles and Neuritic Plaques in Alzheimer's Disease: A Quantitative Study of Visual and Auditory Cortices

    In area 17, 79% of NP were of the NPc type.

    “Nearly 80% of the NP in area 17 was of the NPc type”
    • Also stated in: § Neuritic plaques · plain
      “In area 17, 79% of the NP were of the NPc type”
    Quote in the paperSubstantial claim
  • Findingown data

    Mean NFT number in area 17 was 0.9 (SEM 1.0) per 250-μm-wide cortical traverse.

    “the mean (* SEM) number of NFT in area 17 (primary visual cortex) was very low (0.9 + 1.0).”
    Quote in the paperSubstantial claim
  • Findingown data

    NFT number increased 20-fold from area 17 to area 18.

    “there was a 20-fold increase in the number of NFT (19.7 + 3.6).”
    Quote in the paperSubstantial claim
  • Findingown data
    § Laminar and Regional Distributions of Neurofibrillary Tangles and Neuritic Plaques in Alzheimer's Disease: A Quantitative Study of Visual and Auditory Cortices

    NP showed different and less specific regional and laminar distribution patterns than NFT.

    “In contrast, NP showed different, and less specific, regional and laminar distribution patterns.”
    • Also stated in: § Neuritic plaques · plain
      “The regional and laminar distributions of NP were different from, and less specific than, those of NFT.”
    Quote in the paperSubstantial claim
  • Findingown data
    § Laminar and Regional Distributions of Neurofibrillary Tangles and Neuritic Plaques in Alzheimer's Disease: A Quantitative Study of Visual and Auditory Cortices

    In area 18, layer III contained 79% of the NFT in layers III and V.

    “Layer Ill contained 79% of the NFT in layers Ill and V in area 18”
    • Also stated in: § Neurofibrillary tangles · plain
      “In area 18, layer III contained 79% of the NFT in layers III and V”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 21
  • May combine two claims. 22
  • The quote only partly states this claim. 1

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    Findingnone given
    § Laminar and Regional Distributions of Neurofibrillary Tangles and Neuritic Plaques in Alzheimer's Disease: A Quantitative Study of Visual and Auditory Cortices

    In area 20, 76% of NP were of the NPnc type.

    “over 70% of the NP in both areas 18 and 21 was of the NPnc type”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Laminar and Regional Distributions of Neurofibrillary Tangles and Neuritic Plaques in Alzheimer's Disease: A Quantitative Study of Visual and Auditory Cortices

    NP were present in every cortical layer but were most numerous in layers III and IV.

    “NP were present in every cortical layer but were most numerous in layers Ill and IV.”
    • Also stated in: § Neuritic plaques · plain
      “NP were present in all cortical layers but were most numerous in layers III (20%) and IV (46%) of area 17 and in layer III of area 18 (59%) and area 20 (56%).”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data
    § Laminar and Regional Distributions of Neurofibrillary Tangles and Neuritic Plaques in Alzheimer's Disease: A Quantitative Study of Visual and Auditory Cortices

    In area 18, 72% of NP were of the NPnc type.

    “over 70% of the NP in both areas 18 and 21 was of the NPnc type”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The distribution of NPnc was slightly skewed toward the supragranular layers, whereas the distribution of NPc was slightly skewed toward the infragranular layers.

    “the distribution ofNPnc was slightly skewed toward the supragranular layers, whereas the distribution ofNPc was slightly skewed toward the infragranular layers.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    A substantial number of NP were present in area 17, a region practically devoid of NFT.

    “Note that a substantial number of NP were present in area 17, a region practically devoid of NFT.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The differences in NFT number among visual areas were evident in each case, except case 4101 where areas 18 and 20 did not differ.

    “These differences among regions were evident in each case, with the exception of number 4101, in which areas 18 and 20 did not differ in NFT number (Table 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Primary sensory regions are not spared pathologically in AD, although they lack NFT.

    “These findings also clearly show that primary sensory regions are not spared pathologically in AD, although they lack NFT.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    Classification error is equally likely in all regions of cortex, but more than 50% of NP in areas 18 and 21, and none in area 17, would have had to be misclassified to account for the observed regional differences.

    “This type of error in classification is equally likely to occur in all regions of cortex, but more than 50% of the NP in areas 18 and 2 1, and none of the NP in area 17, would have had to be misclassified in order to account for the observed regional differences.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Laminar and Regional Distributions of Neurofibrillary Tangles and Neuritic Plaques in Alzheimer's Disease: A Quantitative Study of Visual and Auditory Cortices

    Both NFT and NP are thought to be more common in association than in primary sensory or motor regions.

    “both NFT and NP are thought to be more common in association than in primary sensory or motor regions (for reviews, see Terry and Katzman, 1983;Kemper, 1984;Perry, 1986).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Terry and Katzman, 1983

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    • cites Kemper, 1984

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    • cites Perry, 1986

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    Premisecitation
    § Laminar and Regional Distributions of Neurofibrillary Tangles and Neuritic Plaques in Alzheimer's Disease: A Quantitative Study of Visual and Auditory Cortices

    In the cerebral cortex, NFT appear to develop primarily in the cell bodies of pyramidal neurons.

    “In the cerebral cortex, NFT appear to develop primarily in the cell bodies of pyramidal neurons”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Terry and Katzman, 1983

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    • cites Kemper, 1984

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    • cites Perry, 1986

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    Premisecitation
    § Laminar and Regional Distributions of Neurofibrillary Tangles and Neuritic Plaques in Alzheimer's Disease: A Quantitative Study of Visual and Auditory Cortices

    NP are composed of dystrophic neurites and glial processes, with or without an amyloid core.

    “NP are composed of dystrophic neurites and glial processes, with or without an amyloid core (Terry and Wisniewski, 1970).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Terry and Wisniewski, 1970

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    Premisecitation
    § Laminar and Regional Distributions of Neurofibrillary Tangles and Neuritic Plaques in Alzheimer's Disease: A Quantitative Study of Visual and Auditory Cortices

    NFT represent the accumulation of abnormal paired helical filaments in the cytoplasm of neurons.

    “NFT represent the accumulation of abnormal paired helical filaments in the cytoplasm of neurons”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Terry and Wisniewski, 1970

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  • May combine two claims.

    Premisecitation

    The immediately adjacent visual association cortex has a substantially greater number of both types of long efferent projections, and the number of such projections increases even more in the higher-order visual association cortex of the inferior temporal lobe.

    “The immediately adjacent visual association cortex has a substantially greater number of both types of long efferent projections, and the number of such projections increases even more in the higher-order visual association cortex of the inferior temporal lobe (Cragg and Ainsworth, 1969;Zeki, 1969;Jones and Powell, 1970).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Cragg and Ainsworth, 1969

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    • cites Zeki, 1969

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    • cites Jones and Powell, 1970

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    Study design and conductcitation

    Cytoarchitectonic regions were identified according to published criteria.

    “Cytoarchitectonic regions (Fig. 1) were identified according to published criteria (Brodmann, 1909;Bailey and Von Bonin, 1951).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Brodmann, 1909

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    • cites Bailey and Von Bonin, 1951

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    Study design and conductreasoning

    In Thioflavine S-stained material, NFT are evident as fluorescent material in the perinuclear cytoplasm and proximal processes of neurons, whereas NP appear as the accumulation of fluorescent fibrous material, with or without a dense, brightly fluorescent core.

    “Thus, in Thioflavine S-stained material, NFT are evident as fluorescent material in the perinuclear cytoplasm and proximal processes of neurons (Fig. 2), whereas NP appear as the accumulation of fluorescent fibrous material, with or without a dense, brightly fluorescent core (Fig. 5).”
    Quote in the paperNot a substantial claim

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    Premisecitation

    In the visual system, primary visual cortex has very few distant ipsilateral efferent projections and even fewer contralateral projections.

    “in the visual system, primary visual cortex has very few distant ipsilateral efferent projections and even fewer contralateral projections (Tigges et al., 1981;Swadlow, 1983).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Tigges et al., 1981

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    • cites Swadlow, 1983

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    Study design and conductnone given

    Stained structures remain clearly visible even after prolonged exposures under the fluorescent microscope, despite some quenching of fluorescence.

    “Although some quenching of the fluorescence occurs, stained structures remain clearly visible even after prolonged exposures under the fluorescent microscope.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Thioflavine S is a fluorescent stain that visualizes both extracellular amyloid and intracellular paired helical filaments.

    “Thioflavine S is a fluorescent stain that visualizes both extracellular amyloid and intracellular paired helical filaments.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Schwartz, 1972

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    Premisecitation

    The prosomatostatin-derived peptide (PSDP) system of the cortex is profoundly altered in AD, as reflected in decreased tissue levels of PSDP, the presence of PSDP-immunoreactive profiles in NP, and a reduction in PSDP receptor number.

    “The prosomatostatin-derived peptide (PSDP) system of the cortex is profoundly altered in AD, as reflected in decreased tissue levels of PSDP (Davies et al., 1980;Rossor et al., 1980), the presence of PSDP-immunoreactive profiles in NP (Armstrong et al., 1985;Morrison et al., 1985) and a reduction in PSDP receptor number (Beal et al., 1985).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Davies et al., 1980

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    • cites Rossor et al., 1980

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    • cites Armstrong et al., 1985

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    Premisecitation

    The neurotransmitter utilized in corticocortical circuits is believed to be an excitatory amino acid.

    “The neurotransmitter utilized in corticocortical circuits is believed to be an excitatory amino acid (Baughman and Gilbert, 198 1; Fonnum et al.,198 1;Hicks and Geddes,198 1).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Baughman and Gilbert, 1981

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    • cites Fonnum et al., 1981

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    • cites Hicks and Geddes, 1981

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    Premisecitation

    Primary auditory cortex was reported to have fewer NFT than the surrounding auditory association regions.

    “in a recent nonquantitative study, primary auditory cortex was reported to have fewer NFT than the surrounding auditory association regions (Esiri et al., 1986).”
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    • cites Esiri et al., 1986

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    There were more NFT in area 18 than in area 17, and the ratio of NFT in layer III to layer V was greater in area 18 than in area 21.

    “This group also found that there were more NFT in area 18 than in area 17, and that the ratio of NFT in layer III to layer V was greater in area 18 than in area 21 (Pearson et al., 1985).”
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    • cites Pearson et al., 1985

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    Premisecitation

    Layer V pyramidal neurons also give rise to many corticofugal fibers, in addition to corticocortical projections.

    “layer V pyramidal neurons also give rise to many corticofugal fibers, in addition to corticocortical projections (Jones, 198 1,1984).”
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    • cites Jones, 1981, 1984

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    Premisecitation

    In AD, there is loss of both glutamate and aspartate receptors in the neocortex, a profound decrease in glutamate levels in the terminal field of the perforant pathway, and the presence of NFT in glutamate-immunoreactive neurons.

    “Recent studies have demonstrated in AD the loss of both glutamate (Greenamyre et al., 1985) and aspartate (Palmer et al., 1986) receptors in the neocortex, a profound decrease in glutamate levels in the terminal field of the perforant pathway (Hyman et al., 1986) and the presence of NFT in glutamate-immunoreactive neurons (Maragos et al., 1986).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Greenamyre et al., 1985

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    • cites Palmer et al., 1986

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    • cites Hyman et al., 1986

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    Premisecitation

    Cortical levels of neuropeptide Y and GABA are not decreased in AD.

    “cortical levels of neuropeptide Y and GABA, both of which have been shown to coexist with PSDP in cortical neurons (Hendry et al., 1984a, b;Somogyi et al., 1984), are not decreased in AD (Smith et al., 1983;Allen et al., 1984;Perry et al., 1984;Dawbarn et al., 1986).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Smith et al., 1983

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    • cites Allen et al., 1984

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    • cites Perry et al., 1984

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    Premisecitation

    The density of cortical PSDP-containing neurons is normal in AD.

    “the density of cortical PSDP-containing neurons has recently been reported to be normal in this disorder (Nakamura and Vincent, 1986).”
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    • cites Nakamura and Vincent, 1986

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    Interpretationreasoning

    NP may arise at the terminations of long corticocortical projection neurons, at the terminations of various afferent fibers from the brain stem such as cholinergic or noradrenergic neurons, and from the processes of intrinsic cortical neurons such as those containing PSDP.

    “Thus, NP may arise at the terminations of long corticocortical projection neurons, at the terminations of various afferent fibers from the brain stem, such as those from cholinergic or noradrenergic neurons, and from the processes of intrinsic cortical neurons, such as those containing PSDP.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Cholinergic and catecholaminergic processes have been identified in simian and human cortical NP.

    “Cholinergic and catecholaminergic processes, presumably the terminations of afferents from the brain stem, have been identified in simian and human cortical NP (Kitt et al., 1984(Kitt et al., , 1985;;Armstrong et al., 1986).”
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    • cites Kitt et al., 1984

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    • cites Armstrong et al., 1986

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    Interpretationcitation

    Some NP may arise at the terminations of projections from neurons that contain NFT.

    “some NP may arise at the terminations of projections from neurons that contain NFT (Suzuki and Terry, 1967;Pearson et al., 1985).”
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    • cites Suzuki and Terry, 1967

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    • cites Pearson et al., 1985

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    Premisecitation

    Superior frontal and anterior cingulate regions have a greater density of NP than visual and auditory cortical regions.

    “In addition, in a recent quantitative study, superior frontal and anterior cingulate regions were found to have a greater density of NP than visual and auditory cortical regions (Rogers and Morrison, 1985).”
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    • cites Rogers and Morrison, 1985

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    Premisecitation

    NP-containing fibers immunoreactive for neuropeptides such as PSDP, neuropeptide Y, and substance P have been described in the neocortex from patients with AD.

    “NP-containing fibers immunoreactive for a number of different neuropeptides such as PSDP (Armstrong et al., 1985;Morrison et al., 1985) neuropeptide Y (Chan-Palay et al., 1985;Dawbam and Emson, 1985), and substance P (Armstrong and Terry, 1985) have also been described in the neocortex from patients with AD.”
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    • cites Armstrong et al., 1985

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    • cites Morrison et al., 1985

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    • cites Chan-Palay et al., 1985

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    Premisecitation

    Previous studies reported that the number of NP appeared to be greater in association than in primary sensory regions.

    “Previous studies have reported that the number of NP appeared to be greater in association than in primary sensory regions (for reviews, see Terry and Katzman, 1983;Kemper, 1984).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Terry and Katzman, 1983

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    • cites Kemper, 1984

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  • May combine two claims.

    Interpretationreasoning

    NP have less distinctive distribution patterns, suggesting a more heterogeneous origin.

    “In contrast, NP have less distinctive distribution patterns, suggesting a more heterogeneous origin.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    NP number was also inversely related to age in middle frontal, inferior parietal, and superior temporal regions, though generally less strongly than NFT.

    “Although the correlations were generally not as strong as with NFT, NP number was also inversely related to age in these regions (middle frontal: n = 95, r = -0.345,p < 0.001; inferior parietal: n = 93, r = -0.362,p < 0.001; superior temporal: n = 98, r = -0.260,p < 0.0 1).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites R. D. Terry, unpublished observations

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  • May combine two claims.

    Interpretationreasoning

    Some NP may arise at the terminations of long corticocortical projections whereas others may be formed in the terminal fields of subcortical afferents or intrinsic cortical neurons.

    “For example, some NP may arise at the terminations of long corticocortical projections (Suzuki and Terry, 1967;Pearson et al., 1985) whereas others may be formed in the terminal fields of subcortical afferents or intrinsic cortical neurons.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Suzuki and Terry, 1967

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    • cites Pearson et al., 1985

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    Premisecitation

    In previous investigations, NP were described as immature, mature, or burnt-out based upon their morphological appearance.

    “In previous investigations, NP were described as immature, mature, or burnt-out, based upon their morphological appearance (Terry and Wisniewski, 1970).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Terry and Wisniewski, 1970

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    Premisecitation

    In larger samples, NFT number was inversely related to age in middle frontal and inferior parietal regions but not in superior temporal regions.

    “Similarly, in much larger samples of patients (R. D. Terry, unpublished observations), NFT number was inversely related to age in middle frontal (n = 95, Y = -0.450,p < 0.001) and inferior parietal (n = 93, r = -0.575,p < 0.001) regions but not in the superior temporal regions (n = 98, Y = -0.180,NS).”
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    • cites R. D. Terry, unpublished observations

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    Interpretationcitation

    These findings are consistent with previous observations that younger patients with AD have more severe and widespread histological abnormalities and a more rapidly progressive clinical course.

    “These findings are consistent with previous observations that younger patients with AD have more severe and widespread histological abnormalities (Hubbard and Anderson, 198 1;Mountjoy et al., 1983) and a more rapidly progressive clinical course (Sourander and Sjogren, 1970;Seltzer and Sherwin, 1983).”
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    • cites Hubbard and Anderson, 198 1

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    • cites Mountjoy et al., 1983

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    • cites Sourander and Sjogren, 1970

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  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The different morphologic appearances of NP may reflect different sources of NP formation rather than different stages of NP formation.

    “Instead of representing different stages of NP formation, it may be that the different morphologic appearances of NP reflect different sources of NP formation.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: NP have not been demonstrated to undergo a temporally related series of morphological changes.

  • May combine two claims.

    Study design and conductreasoning

    Given the criteria used in this study for distinguishing NP types, all NPnc were probably correctly classified, but some NPc were likely incorrectly identified as NPnc.

    “Given the criteria utilized in this study for distinguishing these NP types, all NPnc were probably correctly classified, but it is likely that some NPc were incorrectly identified as NPnc.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The findings of this study may provide an anatomical basis for the loss of intellectual functions in AD, consistent with the hypothesis that the dementia of AD results from loss of the structural and functional integrity of the long corticocortical projection systems.

    “The findings of this study may provide an anatomical basis for the loss of intellectual functions in AD, in that they are consistent with the hypothesis that the dementia of AD results from the loss of the structural and functional integrity of the long corticocortical projection systems (Pearson et al., 1985;Rogers and Morrison, 1985;Morrison et al., 1986a).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Pearson et al., 1985

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    • cites Rogers and Morrison, 1985

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    • cites Morrison et al., 1986a

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    • Rests on an assumption: The dementia of AD involves a progressive, global deterioration of intellectual functions, abilities which appear to require the integration of information across many specialized regions of cerebral cortex.
41 of 41

  • The paper relies on this without support.

    The precise elements of cortical circuitry compromised by the pathological changes of AD have remained obscure.

    “However, the precise elements of cortical circuitry compromised by these pathological changes have remained obscure.”

  • The paper relies on this without support.

    The distribution of long corticocortical projection neurons in monkey neocortex is homologous to that in human neocortex.

    “in homologous regions of monkey neocortex”
    “in homologous regions of monkey cortex”

  • The paper relies on this without support.

    NFT and NP are the histological hallmarks of Alzheimer's disease.

    “Neurofibrillary tangles (NFT) and neuritic plaques (NP) are the histological hallmarks of Alzheimer's disease (AD).”

  • The paper relies on this without support.

    NP have not been demonstrated to undergo a temporally related series of morphological changes.

    “However, NP have not been demonstrated to undergo a temporally related series of morphological changes.”

  • The paper relies on this without support.

    The dementia of AD involves a progressive, global deterioration of intellectual functions, abilities which appear to require the integration of information across many specialized regions of cerebral cortex.

    “The dementia of AD involves a progressive, global deterioration of intellectual functions, abilities which appear to require the integration of information across many specialized regions of cerebral cortex.”

  • The paper relies on this without support.

    Regions of monkey neocortex are homologous to human neocortex for comparing NFT distribution.

    “in homologous regions of monkey neocortex”
6 of 6

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Neurofibrillary tangles selectively affect highly connected pyramidal cells in association cortex but not in primary sensory cortex.

    “Cognitive impairment correlates with the number of neurofibrillary tangles137, which selectively affect highly connected pyramidal cells in association cortex but not in primary sensory cortex6,138,139.”

    From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [139]

    The Neurofibrillary tangles section reports that tangles were predominantly in pyramidal neurons and were much more numerous in visual and auditory association cortex than in primary sensory cortex. The Discussion links their distribution to neurons with long corticocortical projections, but presents that cell-type link as a hypothesis. The claim's absolute exclusion of primary sensory cortex is unsupported: the study counted small numbers of tangles in both primary visual and primary auditory cortex. (LLM, conf=0.91)

    Experimental — accuracy not yet measured

  • Neurofibrillary tangles exhibit the same regional pattern as neurodegeneration.

    “In contrast, NFTs exhibit the same regional pattern as neurodegeneration(Braak and Braak, 1991; Bussière et al., 2003; Lewis et al., 1987).”

    From Selective Neuronal Vulnerability in Alzheimer’s Disease: A Network-Based Analysis (2020) · cites this paper as Lewis et al., 1987

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Plaque-type finding names area 21 instead of area 20

    Minor

    The abstract assigns the NPnc finding to areas 18 and 21, but the Results assign it to areas 18 and 20; area 20 is the visual region analyzed in the study.

  • Figure 4 reports six cases for a region examined in five

    Minor

    Figure 4 includes area 22 and says its bars represent data from six cases, while the Results state that five auditory-region cases were examined.

  • Area 18 NFT uncertainty differs between abstract and Results

    Minor

    The abstract gives 3.8 alongside the area 18 mean, whereas the Results give 3.6 for the same quantity.

3 of 3

The citation lists haven’t been fetched yet

References 57 · Cited by 578

Research works printed but not linked: 11

  1. Bailey, P., and G. Von Bonin (195 1) The Zsocortex ofMun, University of Illinois Press, Urbana, IL.
  2. I ,II Jones, E. G. (1984) Laminar distribution of cortical efferent cells. In Cerebral Cortex, Vol. 1, A. Peters and E. G. Jones, eds., pp. 521- 553, Plenum, New York.
  3. Kemper, T. (1984) Neuroanatomical and neuropathological changes in normal aging and dementia. In Clinical Neurology of-Aging, M-L. Albert. ed.. DD. 9-52. Oxford U. P.. New York.
  4. Morrison, J. H., S. Scherr, D. A. Lewis, M. J. Campbell, F. E. Bloom, J. Rogers, and R. Benoit (1986a) The laminar and regional distri- bution of neocortical somatostatin and neuritic plaques: Implications for Alzheimer's disease as a global neocortical disconnection syn- drome. In The Biological Substrates of Alzheimer's Disease, A. B. Scheibel and A. F. Weschler, eds., pp. 115-l 3 1, Academic, New York.
  5. Pandya, D. N., and E. H. Yeterian (1985) Architecture and connec- tions ofcortical association areas. In Cerebral Cortex, Vol. 4, A. Peters and E. G. Jones, eds., pp. 3-61, Plenum, New York.
  6. Rosner, B. (1982) Fundamentals OfBiostatistics, Duxbury Press, Bos- ton.
  7. Terry, R. D., and R. Katzman (1983) Senile dementia of the Alzheimer type: Defining a disease. In Neurology of Aging, R. Katzman and R. D. Terry, eds., pp. 51-84, Davis, Philadelphia, PA.
  8. Terry, R. D., and H. M. Wisniewski (1970) The ultrastructure of neurofibrillary tangles and senile plaques. In Alzheimer's Disease and Related Conditions, G. E. W. Wolstenholme and M. O'Connor, eds., pp. 145-165, Churchill, London.
  9. Tigges, J., and M. Tigges (1985) Subcortical sources of direct projec- tions to visual cortex. In Cerebral Cortex, Vol. 3, A. Peters and E. G. Jones, eds., pp. 351-378, Plenum, New York.
  10. Valverde, F. (1985) The organizing principles of the primary visual cortex in the monkey. In Cerebral Cortex, Vol. 3, A. Peters and E. G. Jones, eds., pp. 207-257, Plenum, New York.
  11. Van Essen, D. C. (1985) Functional organization of primate visual cortex. In Cerebral Cortex, Vol. 3, A. Peters and E. G. Jones, eds., pp. 259-330, Plenum, New York.

Authors
Lewis, D., Campbell, M., Terry, R., & Morrison, J.
Affiliations
Scripps Research Institute (US)
ORCID
Morrison, JH
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
1987-06-01
Volume
7
Issue
6
Pages
1799-1808
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.07-06-01799.1987
PMC
PMC6568896
OpenAlex
W1821885973
Semantic Scholar
f1fde4b80fca17539bda75844c5e0cf05f857434
Cited by
578
References
57
Citations by year
2026: 9 · 2025: 8 · 2024: 6 · 2023: 15 · 2022: 9 · 2021: 6 · 2020: 16 · 2019: 10 · 2018: 12 · 2017: 12 · 2016: 10 · 2015: 13 · 2014: 13 · 2013: 12 · 2012: 9
FWCI
20.23
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • John D. and Catherine T. MacArthur Foundation
  • National Institute on Alcohol Abuse and Alcoholism (AA 07456)
  • National Institute on Aging (AG05131)
  • National Institute of Mental Health (MH-00519)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, neurofibrillary tangles, neuritic plaques, thioflavine S, visual cortex, auditory cortex, cortical layers, laminar distribution, visual association cortex, auditory association cortex, pyramidal neurons
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Auditory Cortex, Humans, Middle Aged, Neurofibrils, Staining and Labeling, Visual Cortex

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

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