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Cited by 168Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Light and Electron Microscopic Localization of Presenilin-1 in Primate Brain

Open access
Lah, James J., Heilman, Craig J., Nash, Norman R., Rees, Howard D., Yi, Hong, Counts, Scott E., Levey, Allan I.·1997·The Journal of Neuroscience
DOI 10.1523/jneurosci.17-06-01971.1997PMC PMC6793763
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Abstract

Several genes have been implicated in the pathogenesis of early-onset familial Alzheimer’s disease. A majority of the autosomal dominant cases are linked to recently identified mutations in the presenilin-1 gene on chromosome 14. The native presenilin-1 protein in primates has not been well characterized, and its precise localization is unknown. We have studied the native presenilin-1 protein in monkey brain and peripheral tissues by using a monoclonal antibody specific for the N-terminal domain of human presenilin-1. Western blots detect polypeptide species of ∼49 and ∼32 kDa from COS-7 and PC12 cells transfected with full-length human presenilin-1 cDNA and from in vitro translations of the normal human presenilin-1 mRNA. A 32 kDa polypeptide is detected in monkey peripheral tissues, with the highest expression in testis and lung. In all brain regions the 32 kDa band is the predominant form of presenilin-1, and it is found in particulate subfractions. Light microscopic immunocytochemistry reveals presenilin-1 staining in all brain regions, with the strongest labeling in neurons and neuropil. In addition, weaker immunoreactivity is also present in glia and blood vessels. Neuronal staining shows significant variability, with particularly intense labeling of certain cell types, including large neocortical and hippocampal pyramidal neurons, magnocellular basal forebrain neurons, brainstem motoneurons, and some populations of interneurons. By electron microscopic immunocytochemistry, highly selective presenilin-1 staining is seen on the cytoplasmic surfaces of membranous organelles, which suggest localization to the endoplasmic reticulum–Golgi intermediate compartment, a subdomain of the endoplasmic reticulum, and some coated transport vesicles.

AI snapshot

Written from the paper’s full text.

TL;DR

This study characterizes native presenilin-1 (PS1) in monkey brain and peripheral tissues using a new monoclonal antibody against the human PS1 N terminus. It finds widespread neuronal PS1, predominantly as a 32 kDa polypeptide, with ultrastructural localization to the ER-Golgi intermediate compartment, a subdomain of smooth ER, and some coated transport vesicles.

Key findings

  • The rat monoclonal antibody recognized an epitope between PS1 residues 21–70 and showed no detectable cross-reactivity with the PS2 N terminus.
  • Western blots detected ~49 and ~32 kDa PS1 species in transfected COS-7/PC12 cells and in vitro translations; in monkey brain all regions showed a predominant 32 kDa band and a much fainter ~49 kDa band. Peripheral tissues also showed only the 32 kDa band, with highest levels in testis and lung and no detectable PS1 in pancreas or skeletal muscle.
  • Light microscopic immunocytochemistry revealed PS1 in all brain regions, strongest in neurons and neuropil, with weaker labeling in glia and blood vessels. Intense staining was seen in large neocortical and hippocampal pyramidal neurons, magnocellular basal forebrain neurons, brainstem motoneurons, and some interneurons; cerebellar Purkinje cells showed only low staining.
  • Electron microscopy showed highly selective PS1 staining on cytoplasmic surfaces of membranous organelles, suggesting localization to the ER-Golgi intermediate compartment, a subdomain of smooth ER, and some coated transport vesicles; the vast majority of synaptic vesicles were unlabeled.

Methods

  • A rat monoclonal antibody was generated against GST-PS1 21–80 and characterized by Western blotting, in vitro translation, and transfected COS-7 and PC12 cells.
  • Rhesus monkeys (n = 4) were perfused and processed for light and electron microscopic immunocytochemistry; monkey peripheral tissues and brain regions were analyzed by Western blotting.
  • Subcellular fractionation of monkey cortex used sucrose gradient centrifugation, with PS1 distribution compared with synaptophysin by immunoblotting.

Limitations

  • The paper states that more specific immunoblot localization of PS1 will require comparison of its distribution relative to other organelle-specific markers.
  • The antibody does not recognize the rat PS1 homolog, so it does not detect PS1 in untransfected PC12 cells or rat brain, limiting rodent comparisons.
  • Evident from the text: the primate immunocytochemical sample was small (n = 4), and some labeled coated vesicles were somewhat indistinct because of diaminobenzidine reaction products on cytoplasmic membrane surfaces.

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

Integrity signals

Registry

Crossref · 10.1523/jneurosci.17-06-01971.1997

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 65 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    No endogenous PS1 immunoreactivity is detectable in untransfected PC12 cells.

    “In contrast, no endogenous PS1 immunoreactivity was detectable in untransfected PC12 cells.”
    Quote in the paperNot a substantial claim
  • Findingown data

    In all monkey tissues in which PS1 was detected, the antibody recognized a predominant band that comigrated with the 32 kDa band in PS1-transfected COS-7 cells.

    “In all tissues in which PS1 was detected, the antibody recognized a predominant band that comigrated with the 32 kDa band in PS1-transfected COS-7 cells (Fig. 2, left panel ).”
    Quote in the paperNot a substantial claim
  • Findingown data

    There were only slight differences in PS1 band intensity across different monkey brain regions.

    “There were only slight differences in the band intensity across different brain regions.”
    Quote in the paperSubstantial claim
  • Findingown data

    On overexposed blots, a 32 kDa protein is detectable in untransfected COS-7 cells at much lower levels than in transfected cells.

    “On overexposed blots, a 32 kDa protein was detectable in untransfected COS-7 cells but at much lower levels than in the transfected cells.”
    Quote in the paperNot a substantial claim
  • Findingown data

    In COS-7 cells transiently transfected with PS1 cDNA, the dominant immunoreactive species are a doublet at 49 kDa and a 32 kDa polypeptide.

    “In COS-7 cells transiently transfected with PS1 cDNA, the dominant immunoreactive species were a doublet at 49 kDa and a 32 kDa polypeptide.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 36
  • Classified as probably not a substantial claim. 23
  • The quote only partly states this claim. 2

  • May combine two claims.

    Findingown data

    Less intense immunoreactive bands of approximately 32 and 26 kDa are present in PS1 translation products, and expression of each is facilitated by microsomes.

    “Less intense immunoreactive bands of ϳ32 and ϳ26 kDa were also present in the PS1 translation products.Expression of each of these polypeptides was facilitated by the introduction of microsomes (Fig. 1 B).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The antibody detected PS1 immunoreactivity in all monkey brain regions, primarily as a 32 kDa polypeptide, with a much fainter band at approximately 49 kDa.

    “Our antibody detected PS1 immunoreactivity in all brain regions, primarily as a 32 kDa polypeptide, and labeled a much fainter band at ϳ49 kDa (Fig. 3A).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    An additional prominent band at approximately 95 kDa in skeletal muscle and lung is nonspecific, as it is not eliminated by preadsorption.

    “An additional prominent band migrating at ϳ95 kDa was seen in skeletal muscle and lung samples (Fig. 2, asterisk).However, preadsorption of the primary antibody failed to eliminate this band, indicating that it represents a nonspecific band produced by the detection system.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In PC12 cells stably transfected with human PS1 cDNA, the antibody reacts strongly with a 49 kDa protein and a more abundant 32 kDa polypeptide.

    “The monoclonal antibody reacted strongly with both a 49 kDa protein and a more abundant 32 kDa polypeptide in PC12 cells stably transfected with the human PS1 cDNA.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In monkey tissue samples, only the 32 kDa band was seen; the full-length approximately 49 kDa protein was not detected even when the 32 kDa species was abundant.

    “Although higher molecular weight species, including the presumed full-length protein at ϳ49 kDa, were seen in PS1-transfected COS-7 cells, only the 32 kDa band was seen in the monkey tissue samples.Even in samples in which the 32 kDa species was quite abundant, the full-length protein was not detected.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The monoclonal antibody reacts with human PS1 expressed by in vitro translation of PS1 mRNA, with a major immunoreactive protein at approximately 49 kDa.

    “Western blot analysis also revealed strong antibody reactivity with the human protein expressed by in vitro translation of PS1 mRNA (Fig. 1 B).The major immunoreactive protein was ϳ49 kDa.”
    Quote in the paperSubstantial claim

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

    Findingcitation

    PS1 mRNA and protein are both widespread in peripheral tissues.

    “Although the relative level of PS1 protein does not parallel that of the mRNA exactly, they are both widespread in peripheral tissues.”
    Quote in the paperNot a substantial claim

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

    Findingnone given

    The relative level of PS1 protein does not parallel that of the mRNA exactly.

    “Although the relative level of PS1 protein does not parallel that of the mRNA exactly, they are both widespread in peripheral tissues.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Significant PS1 immunoreactivity persisted in the washed nuclear pellet (P1), whereas synaptophysin did not; synaptophysin remained faintly detectable in the high-speed supernatant (S3), whereas PS1 did not.

    “Significant PS1 immunoreactivity persisted in the washed nuclear pellet, whereas synaptophysin immunoreactivity did not (Fig. 3B, P1).Conversely, synaptophysin remained faintly detectable in the high-speed supernatant (Fig. 3B, S3), whereas PS1 did not.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Rarely, the cis-Golgi stacks were labeled, but the remainders of the Golgi stacks were devoid of immunoreactivity.

    “Rarely, the cis-Golgi stacks were labeled (Fig. 6C), but the remainders of the Golgi stacks were devoid of immunoreactivity (Figs. 6 D,E, 7A).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    PS1-labeled vesicles were not exclusive to neurons or the Golgi apparatus; a forming coated pit in an endothelial cell had adjacent PS1-immunoreactive vesicles.

    “It should be noted that PS1-labeled vesicles were not exclusive to neurons or the Golgi apparatus.Figure 7B shows a forming coated pit in an endothelial cell (asterisk) with adjacent PS1-immunoreactive vesicles (arrowheads).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Select neurons, including large pyramidal neurons in deep layers of frontal cortex, magnocellular basal forebrain neurons, and motor neurons of brainstem nuclei, showed intense PS1 immunoreactivity.

    “Select neurons in a number of brain regions, including pyramidal neurons in layers 3 and 5 of cerebral cortex (Fig. 5A), displayed dramatic staining for PS1.In particular, large pyramidal neurons in the deep layers of frontal cortex frequently stained intensely (Fig. 5A,C, arrows).Other large neurons, including magnocellular basal forebrain neurons (Fig. 5D) and motor neurons of brainstem nuclei (”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The vast majority of synaptic vesicles was unlabeled, and clusters of presynaptic vesicles at synaptic junctions apposed to postsynaptic densities generally lacked PS1 staining.

    “The vast majority of synaptic vesicles was unlabeled, and clusters of presynaptic vesicles at synaptic junctions apposed to postsynaptic densities generally lacked PS1 staining (e.g., Fig. 8 A,B).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Western blots identify a 32 kDa PS1 polypeptide that is widely expressed in brain and peripheral tissues.

    “Western blots identify a 32 kDa PS1 polypeptide that is widely expressed in brain and peripheral tissues.”
    • Also stated in: § Caenorhabditis elegans. · plain
      “PS1 immunoreactivity in tissue homogenates was seen only as a 32 kDa band.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Labeling in presynaptic elements was seen less frequently, but PS1 immunoreactivity was seen occasionally on the cytoplasmic surfaces of some vesicles.

    “Labeling in presynaptic elements was seen less frequently, but PS1 immunoreactivity was seen occasionally on the cytoplasmic surfaces of some vesicles (Fig. 8C,D).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Most labeled membranes possessed a smooth surface, but the PS1 antibody also labeled some coated vesicles near the Golgi and occasionally in continuity with Golgi membranes.

    “Most of the labeled membranes possessed a smooth surface.However, our PS1 antibody also labeled some coated vesicles that were seen near the Golgi and, occasionally, seen in continuity with Golgi membranes (Fig. 6 D,E, arrows).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Virtually all neurons showed some PS1 immunoreactivity, and light staining was also found in glial cells and weak labeling of at least some blood vessels.

    “Although there were considerable differences in the intensity of labeling among cell populations, virtually all neurons showed some PS1 immunoreactivity.Light staining also was found in glial cells (Fig. 5E, arrowheads), and there appeared to be weak labeling of at least some blood vessels (Fig. 5E, asterisk).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In neuronal somata, PS1 antibody produced punctate staining most intense around the nucleus but extended throughout the cell body and into neuronal processes.

    “In neuronal somata, the PS1 antibody produced punctate staining that typically was most intense around the nucleus but extended throughout the cell body (Fig. 5).Moreover, the labeling extended into neuronal processes, and, in some planes of sectioning, immunoreactivity could be followed well into the lengths of both dendrites and axons (Fig. 5C, arrowheads).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    At the ultrastructural level, PS1 immunoreactivity was found in neuronal cell bodies, neuronal processes in the neuropil, glial cells, and some blood vessels.

    “At the ultrastructural level, PS1 immunoreactivity was found in neuronal cell bodies, neuronal processes in the neuropil, glial cells, and some blood vessels.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Within neuronal cell bodies, PS1 was distributed to tubulovesicular profiles, smooth vesicles, coated vesicles, and cis-Golgi stacks; other organelles such as nucleus, rough ER, lysosomes, and mitochondria did not have detectable PS1 immunoreactivity.

    “Within neuronal cell bodies, PS1 was distributed to tubulovesicular profiles, smooth vesicles, coated vesicles, and cis-Golgi stacks; other morphologically identifiable organelles, such as the nucleus, rough ER, lysosomes, and mitochondria, did not have detectable PS1 immunoreactivity.”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    The low-power survey revealed a preponderance of PS1 immunoreactivity in gray matter.

    “The low-power survey revealed a preponderance of immunoreactivity in gray matter.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    PS1 immunoreactivity in glial cells was similar to that in neuronal cell bodies, with labeling on vesicular profiles clustering near the Golgi apparatus.

    “The distribution of PS1 immunoreactivity in glial cells was similar to that in neuronal cell bodies.Labeling was present on vesicular profiles (arrows), which tended to cluster near the Golgi apparatus.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The smaller polypeptide was more abundant in transfected PC12 cells, whereas the larger band predominated in transfected COS-7 cells.

    “The smaller polypeptide was more abundant in transfected PC12 cells, whereas the larger band predominated in transfected COS-7 cells.”
    Quote in the paperNot a substantial claim

  • The quote only partly states this claim.

    Findingown data

    Two primary immunoreactive bands were seen at 49 and 32 kDa in transfected PC12 and COS-7 cells expressing human PS1.

    “Two primary immunoreactive bands were seen at 49 and 32 kDa.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Synaptophysin was present in S3 but undetectable in P1.

    “Conversely, synaptophysin was present in S3, but was undetectable in P1.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The strongest PS1 bands in peripheral tissues were found in testis and lung, whereas PS1 protein was undetectable in pancreas and muscle.

    “The strongest bands were found in testis and lung, whereas PS1 protein was undetectable in pancreas and muscle.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    PS1 immunoreactivity was undetectable in the high-speed supernatant (S3) but was present in the washed nuclear pellet (P1).

    “PS1 immunoreactivity was undetectable in the high-speed supernatant (S3) but was present in the washed nuclear pellet (P1).”
    Quote in the paperSubstantial claim

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

    Findingnone given

    Synthesis of each polypeptide was enhanced by the presence of microsomal membranes.

    “Synthesis of each polypeptide was enhanced by the presence of microsomal membranes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Control lanes from untransfected parent cells did not contain immunoreactive bands, but on overexposed blots the 32 kDa band was seen in untransfected COS-7 cell homogenates.

    “Control lanes from untransfected parent cells (PC12, COS7 ) did not contain immunoreactive bands, but on overexposed blots the 32 kDa band was seen in untransfected COS-7 cell homogenates.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Translation of PS1 mRNA produced a strongly immunoreactive band at ~49 kDa and weaker bands at ~32 and ~26 kDa.

    “Translation of PS1 mRNA produced a strongly immunoreactive band at ϳ49 kDa and weaker bands at ϳ32 and ϳ26 kDa.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Mutations in PS1 seem to alter endoproteolytic processing, leading to abnormal accumulation of the full-length protein.

    “Moreover, mutations in PS1 seem to alter the endoproteolytic processing, lead-ing to an abnormal accumulation of the full-length protein (Mercken et al., 1996;Thinakaran et al., 1996).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Mercken et al., 1996

      Not checked in the free run.

    • cites Thinakaran et al., 1996

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    PS1 protein, as well as mRNA, is present in a variety of nonneural tissues.

    “These results suggest that the PS1 protein, as well as mRNA, is present in a variety of nonneural tissues.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    If PC12 cells express the rat PS1 homolog, then there is divergence between rodent and human species in the region recognized by the antibody.

    “This finding implies that if PC12 cells express the rat PS1 homolog, then there is divergence between rodent and human species in the region recognized by our antibody.”
    Quote in the paperSubstantial claim

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

    Premisecitation
    § Light and Electron Microscopic Localization of Presenilin-1 in Primate Brain

    A majority of autosomal dominant early-onset familial Alzheimer's disease cases are linked to mutations in the presenilin-1 gene on chromosome 14.

    “A majority of the autosomal dominant cases are linked to recently identified mutations in the presenilin-1 gene on chromosome 14.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Sherrington et al., 1995

      Not checked in the free run.

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

    Premisecitation

    The light microscopic distribution of native PS1 in mouse brain and the localization of epitope-tagged presenilins in transfected cells have been reported.

    “The light microscopic distribution of native PS1 in mouse brain (Elder et al., 1996;Moussaoui et al., 1996) and the localization of epitopetagged presenilins in transfected cells (Kovacs et al., 1996) have been reported.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Elder et al., 1996

      Not checked in the free run.

    • cites Moussaoui et al., 1996

      Not checked in the free run.

    • cites Kovacs et al., 1996

      Not checked in the free run.

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

    Premisecitation

    PS1 protein undergoes endoproteolytic cleavage resulting in N- and C-terminal fragments of approximately 27 and 17 kDa, respectively.

    “Recent studies of PS1 protein have revealed endoproteolytic cleavage resulting in N-and C-terminal fragments of ϳ27 and ϳ17 kDa, respectively (Thinakaran et al., 1996).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Thinakaran et al., 1996

      Not checked in the free run.

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

    Premisecitation

    Presenilin-1 and presenilin-2 are highly homologous genes with 67% amino acid identity.

    “Presenilin-1 (PS1) and presenilin-2 (PS2) are highly homologous genes (67% amino acid identity; Levy-Lahad et al., 1995;Rogaev et al., 1995) that encode a novel family of membrane-associated proteins.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Levy-Lahad et al., 1995

      Not checked in the free run.

    • cites Rogaev et al., 1995

      Not checked in the free run.

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

    Premisecitation

    Northern blot and in situ hybridization studies show widespread expression of presenilin mRNAs in brain and peripheral tissues of humans and rodents.

    “Northern blot and in situ hybridization studies of presenilin mRNAs show widespread expression in brain and peripheral tissues of both humans and rodents (Rogaev et al., 1995;Sherrington et al., 1995;Kovacs et al., 1996;Suzuki et al., 1996).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Rogaev et al., 1995

      Not checked in the free run.

    • cites Sherrington et al., 1995

      Not checked in the free run.

    • cites Kovacs et al., 1996

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    PS1 was found at similar levels throughout the monkey brain, suggesting a role in general neuronal function rather than a region- or cell type-specific activity.

    “was found at similar levels throughout the monkey brain, suggesting a role in general neuronal function rather than a region-or cell type-specific activity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    The pattern of PS1 immunoreactivity in monkey brain is heterogeneous, and some of the more intensely stained neurons correspond to vulnerable populations affected in Alzheimer's disease.

    “The pattern of PS1 immunoreactivity in monkey brain is heterogeneous, and some of the more intensely stained neurons correspond to vulnerable populations affected in AD (Terry et al., 1981;Hof et al., 1990).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Terry et al., 1981

      Not checked in the free run.

    • cites Hof et al., 1990

      Not checked in the free run.

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

    Premisecitation

    The highest levels of PS1 mRNA have been found in testis.

    “It is noteworthy that the highest levels of both PS1 mRNA (Suzuki et al., 1996) and protein (Fig. 2) have been found in testis.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Suzuki et al., 1996

      Not checked in the free run.

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

    Premisecitation

    Original reports of PS1 and PS2 transcription in a variety of tissues have been confirmed by subsequent Northern blot and in situ hybridization studies.

    “The original reports of PS1 and PS2 transcription in a variety of tissues (Rogaev et al., 1995;Sherrington et al., 1995), have been confirmed by subsequent Northern blot and in situ hybridization studies (Kovacs et al., 1996;Sahara et al., 1996;Suzuki et al., 1996).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Rogaev et al., 1995

      Not checked in the free run.

    • cites Sherrington et al., 1995

      Not checked in the free run.

    • cites Kovacs et al., 1996

      Not checked in the free run.

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

    Premisecitation

    The only known genes with significant homology to the presenilins are spe-4 and sel-12 from C. elegans.

    “The only known genes with significant homology to the presenilins are spe-4 (L'Hernault and Arduengo, 1992) and sel-12 (Levitan and Greenwald, 1995)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites L'Hernault and Arduengo, 1992

      Not checked in the free run.

    • cites Levitan and Greenwald, 1995

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The pattern of immunoreactivity in cell bodies reveals a specific association with a population of transport vesicles and indicates a distribution in the ER-Golgi intermediate compartment.

    “The pattern of immunoreactivity in cell bodies reveals a specific association with a population of transport vesicles and indicates a distribution in the ER-Golgi intermediate compartment (Hauri and Schweizer, 1992;Rexach et al., 1994;Krijnse-Locker et al., 1995).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Hauri and Schweizer, 1992

      Not checked in the free run.

    • cites Rexach et al., 1994

      Not checked in the free run.

    • cites Krijnse-Locker et al., 1995

      Not checked in the free run.

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

    Premisecitation

    Endoproteolytic cleavage of PS1 resulting in regulated accumulation of N- and C-terminal derivatives has been reported in transgenic mice.

    “Recently, endoproteolytic cleavage of PS1 resulting in regulated accumulation of Nand C-terminal derivatives has been reported in transgenic mice (Thinakaran et al., 1996).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Thinakaran et al., 1996

      Not checked in the free run.

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

    Premisecitation

    Endoproteolytic cleavage of PS1 is suspected to occur between amino acid residues 260-320 in or near the proximal loop domain.

    “The endoproteolytic cleavage of PS1 is suspected to occur between amino acid residues 260 -320 in or near the proximal loop domain (Thinakaran et al., 1996).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Thinakaran et al., 1996

      Not checked in the free run.

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

    Premisecitation

    Neurons in the brainstem and spinal cord showed more prominent staining in the cell body and axon (Elder et al., 1996).

    “Neurons in the brainstem and spinal cord showed more prominent staining in the cell body and axon (Elder et al., 1996).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Elder et al., 1996

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Reports indicate that mutations in the presenilins affect the processing and secretion of Aβ peptide.

    “These indications of a role for PS1 in intracellular transport are even more intriguing when considered in light of reports that mutations in the presenilins affect the processing and secretion of A␤ peptide (Martins et al., 1995;Borchelt et al., 1996;Duff et al., 1996;Scheuner et al., 1996).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Martins et al., 1995

      Not checked in the free run.

    • cites Borchelt et al., 1996

      Not checked in the free run.

    • cites Duff et al., 1996

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    The SER in neurons has been characterized as an intricate communicating network that extends from the cell body into the terminal segments of dendritic and axonal processes.

    “The SER in neurons has been characterized as an intricate communicating network that extends from the cell body into the terminal segments of dendritic and axonal processes (Broadwell and Cataldo, 1984;Terasaki et al., 1994).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Broadwell and Cataldo, 1984

      Not checked in the free run.

    • cites Terasaki et al., 1994

      Not checked in the free run.

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

    Premisecitation

    SPE-4 plays a role in the packaging of major sperm protein during spermatogenesis.

    “The SEL-12 protein has not yet been characterized, but SPE-4 is known to play a role in the packaging of major sperm protein during spermatogenesis (L' Hernault and Arduengo, 1992).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites L'Hernault and Arduengo, 1992

      Not checked in the free run.

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

    Premisecitation

    Elder et al. (1996) reported a marked concentration of PS1 in the apical dendrites of olfactory bulb mitral cells, neocortical pyramidal cells, hippocampal pyramidal cells, and cerebellar Purkinje cells, with much weaker staining of cell bodies and axons in these cells.

    “In contrast, Elder et al. (1996) reported a marked concentration of PS1 in the apical dendrites of olfactory bulb mitral cells, neocortical pyramidal cells, hippocampal pyramidal cells, and cerebellar Purkinje cells, with much weaker staining of cell bodies and axons in these cells.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Elder et al., 1996

      Not checked in the free run.

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

    Premisecitation

    In previous immunofluorescence studies, PS1 and PS2 were localized to ER and Golgi in transiently transfected neuroglioma cells overexpressing epitope-tagged proteins.

    “In previous immunofluorescence studies, PS1 and PS2 were localized to ER and Golgi in transiently transfected neuroglioma cells overexpressing epitope-tagged proteins (Kovacs et al., 1996).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kovacs et al., 1996

      Not checked in the free run.

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

    Premisecitation

    A significant body of evidence suggests that these membranes are heterogeneous and contain biochemically and functionally distinct domains, including molecular specializations involved in calcium regulation.

    “Furthermore, a significant body of evidence suggests that these membranes are heterogeneous and contain biochemically and functionally distinct domains, including molecular specializations involved in calcium regulation (Satoh et al., 1990;Takei et al., 1992).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Satoh et al., 1990

      Not checked in the free run.

    • cites Takei et al., 1992

      Not checked in the free run.

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

    Premisecitation

    Two groups have reported immunocytochemical localization of PS1 in rodent brains using polyclonal antibodies raised to synthetic peptides from the large internal loop region of PS1.

    “Recently, two groups have reported immunocytochemical localization of PS1 in rodent brains, using polyclonal antibodies raised to synthetic peptides from the large internal loop region of PS1 (Elder et al., 1996;Moussaoui et al., 1996).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Elder et al., 1996

      Not checked in the free run.

    • cites Moussaoui et al., 1996

      Not checked in the free run.

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

    Premisecitation

    PS1 overexpressed in a neuronal cell line infected with recombinant virions was localized to SER and rough ER by confocal microscopy.

    “More recently, PS1 overexpressed in a neuronal cell line infected with recombinant virions was localized to SER and rough ER by confocal microscopy (Cook et al., 1996).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Cook et al., 1996

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In rodent brains, PS1 immunoreactivity was exclusive to neurons, with no staining in glia or blood vessels.

    “The immunoreactivity in rodent brains was exclusive to neurons, and no staining was seen in glia or blood vessels.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Elder et al., 1996

      Not checked in the free run.

    • cites Moussaoui et al., 1996

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    Preadsorption of the anti-PS1 monoclonal antibody with GST-PS1 21-80 eliminated all staining, demonstrating specificity of the immunocytochemical reaction.

    “Preadsorption of the anti-PS1 monoclonal antibody with GST-PS1 21-80 eliminated all staining, demonstrating the specificity of the immunocytochemical reaction (F ).”
    Quote in the paperSubstantial claim
57 of 57

  • The paper relies on this without support.

    The native presenilin-1 protein in primates has not been well characterized, and its precise localization is unknown.

    “The native presenilin-1 protein in primates has not been well characterized, and its precise localization is unknown.”

  • The paper relies on this without support.

    Alzheimer's disease pathology has species selectivity.

    “Given the species selectivity of AD pathology, a detailed examination of the native proteins in primate brain, including precise subcellular localization, is critical for providing insights into normal presenilin functions and their role in AD.”

  • The paper relies on this without support.

    Mutations in the PS1 gene cause aggressive, early-onset Alzheimer's disease via an unknown mechanism.

    “Mutations in the PS1 gene cause aggressive, early-onset AD via an unknown mechanism.”
3 of 3

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?

  • PS1 localizes particularly to endosomes in distal neurites, including pre- and post-synaptic compartments.

    “Immuno-EM for PS1 localized this critical component of the γ-secretase complex particularly to endosomes in distal neurites, including in both pre- and post-synaptic compartments [94].”

    From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [94]

The citation lists haven’t been fetched yet

References 43 · Cited by 168

Authors
Lah, J. J., Heilman, C. J., Nash, N. R., Rees, H. D., Yi, H., Counts, S. E., & Levey, A. I.
Affiliations
Emory University (US)
ORCID
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
1997-03-15
Volume
17
Issue
6
Pages
1971-1980
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
DOI
10.1523/jneurosci.17-06-01971.1997
PMC
PMC6793763
OpenAlex
W1663198600
Cited by
168
References
43
Citations by year
2025: 1 · 2024: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2017: 1 · 2016: 2 · 2015: 2 · 2014: 1 · 2013: 4 · 2012: 2
FWCI
15.87
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5k08ns001902-05)
  • National Institute of Neurological Disorders and Stroke (NS01902-01)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
presenilin 1, Alzheimer's disease, early-onset familial Alzheimer's disease, presenilin 1 mutations, primate brain, monkey brain, neuronal localization, N-terminal domain, immunocytochemistry, electron microscopy, hippocampal pyramidal neurons, motor neurons, interneurons
MeSH terms
Animals, Brain, Humans, Immunohistochemistry, Macaca, Membrane Proteins, Microscopy, Electron, Presenilin-1

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

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

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