neurofibrillary tangles


Summary: Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) UBIQUITINS. As one of the hallmarks of ALZHEIMER DISEASE, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease.

Top Publications

  1. Chang E, Kim S, Schafer K, Kuret J. Pseudophosphorylation of tau protein directly modulates its aggregation kinetics. Biochim Biophys Acta. 2011;1814:388-95 pubmed publisher
    ..The data suggest that incorporation of negative charge into the T212 site can directly promote tau filament formation at multiple steps in the aggregation pathway. ..
  2. Lesser G, Beeri M, Schmeidler J, Purohit D, Haroutunian V. Cholesterol and LDL relate to neuritic plaques and to APOE4 presence but not to neurofibrillary tangles. Curr Alzheimer Res. 2011;8:303-12 pubmed
    ..HDL)cholesterol directly with the densities of Alzheimer hallmarks--neuritic plaques (NP) and neurofibrillary tangles (NFT)--in nursing home residents (n=281)...
  3. Filipcik P, Zilka N, Bugos O, Kučerák J, Koson P, Novak P, et al. First transgenic rat model developing progressive cortical neurofibrillary tangles. Neurobiol Aging. 2012;33:1448-56 pubmed publisher
    ..b>Neurofibrillary tangles (NFTs) satisfied several key histological criteria used to identify neurofibrillary degeneration in human ..
  4. Iqbal K, Wang X, Blanchard J, Liu F, Gong C, Grundke Iqbal I. Alzheimer's disease neurofibrillary degeneration: pivotal and multifactorial. Biochem Soc Trans. 2010;38:962-6 pubmed publisher
    ..Restoration of PP2A activity by inhibition of the cleavage of I(2)(PP2A)/SET offers a promising therapeutic opportunity in AD with this aetiopathogenic mechanism. ..
  5. Braak H, Zetterberg H, Del Tredici K, Blennow K. Intraneuronal tau aggregation precedes diffuse plaque deposition, but amyloid-? changes occur before increases of tau in cerebrospinal fluid. Acta Neuropathol. 2013;126:631-41 pubmed publisher
    ..with that in which both proteins develop in the brain, where intraneuronal tau inclusions (pretangles, neurofibrillary tangles, neuropil threads) appear decades before the deposition of amyloid-? plaques (diffuse plaques, neuritic ..
  6. Kovacs G, Milenkovic I, Wöhrer A, Hoftberger R, Gelpi E, Haberler C, et al. Non-Alzheimer neurodegenerative pathologies and their combinations are more frequent than commonly believed in the elderly brain: a community-based autopsy series. Acta Neuropathol. 2013;126:365-84 pubmed publisher
    ..This should be considered in diagnostic evaluation of biomarkers, and for better clinical stratification of patients. ..
  7. Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E. Alzheimer's disease. Lancet. 2011;377:1019-31 pubmed publisher
    ..In this Seminar, we provide an overview of recent evidence regarding the epidemiology, pathogenesis, diagnosis, and treatment of Alzheimer's disease, and discuss potential ways to reduce the risk of developing the disease. ..
  8. Garcia Sierra F, Jarero Basulto J, Kristofikova Z, Majer E, Binder L, Ripova D. Ubiquitin is associated with early truncation of tau protein at aspartic acid(421) during the maturation of neurofibrillary tangles in Alzheimer's disease. Brain Pathol. 2012;22:240-50 pubmed publisher
    Pathological processing of tau protein during the formation and maturation of neurofibrillary tangles (NFTs) includes abnormal phosphorylation, conformational changes and truncation of the C-terminus at aspartic-acid(421) (apoptotic ..
  9. Murray M, Graff Radford N, Ross O, Petersen R, Duara R, Dickson D. Neuropathologically defined subtypes of Alzheimer's disease with distinct clinical characteristics: a retrospective study. Lancet Neurol. 2011;10:785-96 pubmed publisher
    ..By use of thioflavin-S fluorescence microscopy, we assessed the density and the distribution of neurofibrillary tangles in three cortical regions and two hippocampal sectors...

More Information


  1. Roher A, Tyas S, Maarouf C, Daugs I, Kokjohn T, Emmerling M, et al. Intracranial atherosclerosis as a contributing factor to Alzheimer's disease dementia. Alzheimers Dement. 2011;7:436-44 pubmed publisher
    ..Our results, combined with a consideration of the multifaceted effects of impaired cerebral circulation, suggest an immediate need for prospective clinical trials to assess the efficacy of AD prevention using antiatherosclerotic agents. ..
  2. Caselli R, Walker D, Sue L, Sabbagh M, Beach T. Amyloid load in nondemented brains correlates with APOE e4. Neurosci Lett. 2010;473:168-71 pubmed publisher
    ..Nondemented APOE e4 carriers over age 60 have a higher burden of total parenchymal and vascular amyloid neuropathology than NC, but no difference in neuritic plaque and NFT pathology. ..
  3. Chambers J, Uchida K, Harada T, Tsuboi M, Sato M, Kubo M, et al. Neurofibrillary tangles and the deposition of a beta amyloid peptide with a novel N-terminal epitope in the brains of wild Tsushima leopard cats. PLoS ONE. 2012;7:e46452 pubmed publisher
    ..Conversely, neurofibrillary tangles (NFT), the other hallmark lesion of Alzheimer's disease (AD), are extremely rare in these animals...
  4. Leroy K, Ando K, Héraud C, Yilmaz Z, Authelet M, Boeynaems J, et al. Lithium treatment arrests the development of neurofibrillary tangles in mutant tau transgenic mice with advanced neurofibrillary pathology. J Alzheimers Dis. 2010;19:705-19 pubmed publisher
    b>Neurofibrillary tangles (NFTs) made of phosphorylated tau proteins are a key lesion of Alzheimer's disease and other neurodegenerative diseases, and previous studies have indicated that lithium can decrease tau phosphorylation in tau ..
  5. Yoshiyama Y, Lee V, Trojanowski J. Therapeutic strategies for tau mediated neurodegeneration. J Neurol Neurosurg Psychiatry. 2013;84:784-95 pubmed publisher
    ..Here we review the strategies for tau directed treatments based on recent progress in research on tau and our understanding of the pathomechanisms of tau mediated neurodegeneration. ..
  6. Gozes I. Tau pathology and future therapeutics. Curr Alzheimer Res. 2010;7:685-96 pubmed
    ..healthy brain and move on to the underling pathology of Alzheimer's disease (AD) with emphasis on tau and neurofibrillary tangles. Tangles have been associated with cognitive dysfunction causing neurodegeneration in the absence of ..
  7. Boimel M, Grigoriadis N, Lourbopoulos A, Haber E, Abramsky O, Rosenmann H. Efficacy and safety of immunization with phosphorylated tau against neurofibrillary tangles in mice. Exp Neurol. 2010;224:472-85 pubmed publisher
    As an abnormally folded and aggregated protein, tau composed of neurofibrillary tangles (NFTs) in Alzheimer's disease and other tauopathies seems to be a candidate for immunotherapy...
  8. Ando K, Brion J, Stygelbout V, Suain V, Authelet M, Dedecker R, et al. Clathrin adaptor CALM/PICALM is associated with neurofibrillary tangles and is cleaved in Alzheimer's brains. Acta Neuropathol. 2013;125:861-78 pubmed publisher
    ..Immunohistochemistry revealed that PICALM was associated in situ with neurofibrillary tangles, co-localising with conformationally abnormal and hyperphosphorylated tau in LOAD, familial AD and Down ..
  9. de Calignon A, Fox L, Pitstick R, Carlson G, Bacskai B, Spires Jones T, et al. Caspase activation precedes and leads to tangles. Nature. 2010;464:1201-4 pubmed publisher
    Studies of post-mortem tissue have shown that the location of fibrillar tau deposits, called neurofibrillary tangles (NFT), matches closely with regions of massive neuronal death, severe cytological abnormalities, and markers of caspase ..
  10. Rudrabhatla P, Jaffe H, Pant H. Direct evidence of phosphorylated neuronal intermediate filament proteins in neurofibrillary tangles (NFTs): phosphoproteomics of Alzheimer's NFTs. FASEB J. 2011;25:3896-905 pubmed publisher
    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by brain pathology of intracellular neurofibrillary tangles (NFTs) and extracellular amyloid plaques...
  11. Braak H, Thal D, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol. 2011;70:960-9 pubmed publisher
    ..Pretangles gradually became argyrophilic neurofibrillary tangles (NFTs) that progressed in parallel with NFT Stages I to VI...
  12. Iba M, Guo J, McBride J, Zhang B, Trojanowski J, Lee V. Synthetic tau fibrils mediate transmission of neurofibrillary tangles in a transgenic mouse model of Alzheimer's-like tauopathy. J Neurosci. 2013;33:1024-37 pubmed publisher
    ..frontotemporal lobar degeneration with tau pathologies, are neurodegenerative diseases characterized by neurofibrillary tangles (NFTs) comprising filamentous tau protein...
  13. Braak H, Del Tredici K. The pathological process underlying Alzheimer's disease in individuals under thirty. Acta Neuropathol. 2011;121:171-81 pubmed publisher
    ..e., before puberty or in early young adulthood. ..
  14. Castellani R, Rolston R, Smith M. Alzheimer disease. Dis Mon. 2010;56:484-546 pubmed publisher
  15. Guo J, Lee V. Seeding of normal Tau by pathological Tau conformers drives pathogenesis of Alzheimer-like tangles. J Biol Chem. 2011;286:15317-31 pubmed publisher
    b>Neurofibrillary tangles (NFTs) in Alzheimer disease and related tauopathies are composed of insoluble hyperphosphorylated Tau protein, but the mechanisms underlying the conversion of highly soluble Tau into insoluble NFTs remain elusive...
  16. Ferrer I. Defining Alzheimer as a common age-related neurodegenerative process not inevitably leading to dementia. Prog Neurobiol. 2012;97:38-51 pubmed publisher
    ..neurodegenerative process distinguished from normal aging by the presence of senile plaques and neurofibrillary tangles. Alzheimer affects about 80% of individuals aged 65 years but dementia only occurs in a small percentage ..
  17. Wang J, Xia Y, Grundke Iqbal I, Iqbal K. Abnormal hyperphosphorylation of tau: sites, regulation, and molecular mechanism of neurofibrillary degeneration. J Alzheimers Dis. 2013;33 Suppl 1:S123-39 pubmed
    ..greater than normal tau, and in this altered state it is aggregated into paired helical filaments forming neurofibrillary tangles, a histopathological hallmark of the disease...
  18. Tremblay M, Acker C, Davies P. Tau phosphorylated at tyrosine 394 is found in Alzheimer's disease tangles and can be a product of the Abl-related kinase, Arg. J Alzheimers Dis. 2010;19:721-33 pubmed publisher
    Tau is a microtubule-associated protein and a main component of neurofibrillary tangles, one of the pathologic hallmarks of Alzheimer's disease...
  19. Serizawa S, Chambers J, Une Y. Beta amyloid deposition and neurofibrillary tangles spontaneously occur in the brains of captive cheetahs (Acinonyx jubatus). Vet Pathol. 2012;49:304-12 pubmed publisher
    Alzheimer disease is a dementing disorder characterized pathologically by A? deposition, neurofibrillary tangles, and neuronal loss...
  20. Karch C, Jeng A, Goate A. Calcium phosphatase calcineurin influences tau metabolism. Neurobiol Aging. 2013;34:374-86 pubmed publisher
    Alzheimer's disease (AD) is characterized by neuronal loss and the accumulation of ?-amyloid plaques and neurofibrillary tangles in the brain...
  21. Polydoro M, de Calignon A, Suarez Calvet M, Sanchez L, Kay K, Nicholls S, et al. Reversal of neurofibrillary tangles and tau-associated phenotype in the rTgTauEC model of early Alzheimer's disease. J Neurosci. 2013;33:13300-11 pubmed publisher
    b>Neurofibrillary tangles (NFTs), a marker of neuronal alterations in Alzheimer's disease (AD) and other tauopathies, are comprised of aggregates of hyperphosphorylated tau protein...
  22. Thangavel R, Van Hoesen G, Zaheer A. The abnormally phosphorylated tau lesion of early Alzheimer's disease. Neurochem Res. 2009;34:118-23 pubmed publisher
    The perirhinal cortex (area 35) is well-known locus for neurofibrillary tangles (NFT) in initial Alzheimer's disease (AD) and fully developed AD and may contain tau alterations in non-demented elderly...
  23. Batra A, Prayson R. Meningioangiomatosis associated with focal cortical dysplasia and neurofibrillary tangles. Clin Neuropathol. 2013;32:37-41 pubmed publisher
    ..Intracytoplasmic neurofibrillary tangles within dysplastic neurons were present throughout the lesion...
  24. Ramirez J, Poulton W, Knelson E, Barton C, King M, Klein R. Focal expression of mutated tau in entorhinal cortex neurons of rats impairs spatial working memory. Behav Brain Res. 2011;216:332-40 pubmed publisher
    ..volume is predictive of AD and two of the hallmark neuroanatomical markers of AD, amyloid plaques and neurofibrillary tangles (NFTs), are particularly prevalent in the entorhinal area of AD-afflicted brains...
  25. Querfurth H, LaFerla F. Alzheimer's disease. N Engl J Med. 2010;362:329-44 pubmed publisher
  26. Takashima A. Tau aggregation is a therapeutic target for Alzheimer's disease. Curr Alzheimer Res. 2010;7:665-9 pubmed
    ..b>Neurofibrillary tangles (NFTs), which contain hyperphosphorylated tau, are another pathological hallmark of AD...
  27. Braithwaite S, Schmid R, He D, Sung M, Cho S, Resnick L, et al. Inhibition of c-Jun kinase provides neuroprotection in a model of Alzheimer's disease. Neurobiol Dis. 2010;39:311-7 pubmed publisher
    ..the three major pathological hallmarks of Alzheimer's disease (AD): development of amyloid plaques, neurofibrillary tangles, and brain atrophy...
  28. Mutsuga M, Chambers J, Uchida K, Tei M, Makibuchi T, Mizorogi T, et al. Binding of curcumin to senile plaques and cerebral amyloid angiopathy in the aged brain of various animals and to neurofibrillary tangles in Alzheimer's brain. J Vet Med Sci. 2012;74:51-7 pubmed
    ..of various animal species and a human patient with Alzheimer's disease (AD), together with its binding to neurofibrillary tangles (NFTs)...
  29. Grinberg L, Wang X, Wang C, Sohn P, Theofilas P, Sidhu M, et al. Argyrophilic grain disease differs from other tauopathies by lacking tau acetylation. Acta Neuropathol. 2013;125:581-93 pubmed publisher
    ..Pathologically, AGD is characterized by neuropil grains, pre-neurofibrillary tangles, and oligodendroglial coiled bodies, all recognized by phospho-tau antibodies...
  30. Castillo Carranza D, Sengupta U, Guerrero Muñoz M, Lasagna Reeves C, Gerson J, Singh G, et al. Passive immunization with Tau oligomer monoclonal antibody reverses tauopathy phenotypes without affecting hyperphosphorylated neurofibrillary tangles. J Neurosci. 2014;34:4260-72 pubmed publisher
    Recent findings suggest that tau oligomers, which form before neurofibrillary tangles (NFTs), are the true neurotoxic tau entities in neurodegenerative tauopathies, including Alzheimer's disease (AD)...
  31. Heneka M, O Banion M, Terwel D, Kummer M. Neuroinflammatory processes in Alzheimer's disease. J Neural Transm (Vienna). 2010;117:919-47 pubmed publisher
  32. de Calignon A, Polydoro M, Suarez Calvet M, William C, Adamowicz D, Kopeikina K, et al. Propagation of tau pathology in a model of early Alzheimer's disease. Neuron. 2012;73:685-97 pubmed publisher
    b>Neurofibrillary tangles advance from layer II of the entorhinal cortex (EC-II) toward limbic and association cortices as Alzheimer's disease evolves...
  33. Piedrahita D, Hernandez I, López Tobón A, Fedorov D, Obara B, Manjunath B, et al. Silencing of CDK5 reduces neurofibrillary tangles in transgenic alzheimer's mice. J Neurosci. 2010;30:13966-76 pubmed publisher
    ..Furthermore, the knockdown of CDK5 strongly decreased the number of neurofibrillary tangles in the hippocampi of triple-transgenic mice (3×Tg-AD mice)...
  34. Johnson V, Stewart W, Smith D. Widespread ? and amyloid-? pathology many years after a single traumatic brain injury in humans. Brain Pathol. 2012;22:142-9 pubmed publisher
    ..uninjured, age-matched controls (n=47) were examined for neurofibrillary tangles (NFTs) and amyloid-? (A?) plaques using immunohistochemistry and thioflavine-S staining...
  35. Congdon E, Duff K. Is tau aggregation toxic or protective?. J Alzheimers Dis. 2008;14:453-7 pubmed
    ..Indeed, if monomeric or oligomeric species are mediators of disease, formation of larger tau filaments may prove beneficial to affected cells. This review will examine the findings regarding the toxicity of various tau species. ..
  36. Nelson P, Abner E, Scheff S, Schmitt F, Kryscio R, Jicha G, et al. Alzheimer's-type neuropathology in the precuneus is not increased relative to other areas of neocortex across a range of cognitive impairment. Neurosci Lett. 2009;450:336-9 pubmed publisher
    ..vulnerable to AD-type pathological lesions (diffuse amyloid plaques, neuritic amyloid plaques, and neurofibrillary tangles)...
  37. Pei J, Sjogren M, Winblad B. Neurofibrillary degeneration in Alzheimer's disease: from molecular mechanisms to identification of drug targets. Curr Opin Psychiatry. 2008;21:555-61 pubmed publisher
    ..The processes of tau hyperphosphorylation and the formation of neurofibrillary tangles are caused by the imbalance of the activities of protein kinases and protein phosphatases in Alzheimer's ..
  38. Fonseca M, Ager R, Chu S, Yazan O, Sanderson S, LaFerla F, et al. Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer's disease. J Immunol. 2009;183:1375-83 pubmed publisher
    Alzheimer's disease (AD) is an age-related dementia, characterized by amyloid plaques, neurofibrillary tangles, neuroinflammation, and neuronal loss in the brain...
  39. Mo Z, Zhu Y, Zhu H, Fan J, Chen J, Liang Y. Low micromolar zinc accelerates the fibrillization of human tau via bridging of Cys-291 and Cys-322. J Biol Chem. 2009;284:34648-57 pubmed publisher
    A hallmark of a group of neurodegenerative diseases such as Alzheimer disease is the formation of neurofibrillary tangles, which are principally composed of bundles of filaments formed by microtubule-associated protein Tau...
  40. Snider B, Fagan A, Roe C, Shah A, Grant E, Xiong C, et al. Cerebrospinal fluid biomarkers and rate of cognitive decline in very mild dementia of the Alzheimer type. Arch Neurol. 2009;66:638-45 pubmed publisher
    ..Biomarkers of CSF may be useful prognostically and to identify individuals who are more likely to progress for participation in therapeutic clinical trials. ..
  41. Ding H, Dolan P, Johnson G. Histone deacetylase 6 interacts with the microtubule-associated protein tau. J Neurochem. 2008;106:2119-30 pubmed publisher vitro and in vivo evidence that HDAC6 interacts with tau, a microtubule-associated protein that forms neurofibrillary tangles in Alzheimer's disease...
  42. Arvanitakis Z, Grodstein F, Bienias J, Schneider J, Wilson R, Kelly J, et al. Relation of NSAIDs to incident AD, change in cognitive function, and AD pathology. Neurology. 2008;70:2219-25 pubmed publisher
    ..AD pathology was summarized as a global measure and as measures of neuritic plaques, diffuse plaques, and neurofibrillary tangles. We used Cox proportional hazards models and mixed models for incident AD and cognitive decline, ..
  43. Sugata H, Matsuo K, Nakagawa T, Takahashi M, Mukai H, Ono Y, et al. A peptidyl-prolyl isomerase, FKBP12, accumulates in Alzheimer neurofibrillary tangles. Neurosci Lett. 2009;459:96-9 pubmed publisher
    ..Furthermore, numerous intracellular neurofibrillary tangles (NFTs) were stained for FKBP12 in the hippocampal CA1 subfield, subiculum, entorhinal cortex and angular ..
  44. Price J, McKeel D, Buckles V, Roe C, Xiong C, Grundman M, et al. Neuropathology of nondemented aging: presumptive evidence for preclinical Alzheimer disease. Neurobiol Aging. 2009;30:1026-36 pubmed publisher
    ..Senile plaques (SPs) and neurofibrillary tangles (NFTs) were assessed quantitatively in 97 cases from 7 Alzheimer's Disease Centers (ADCs)...
  45. Sigurdsson E. Tau-focused immunotherapy for Alzheimer's disease and related tauopathies. Curr Alzheimer Res. 2009;6:446-50 pubmed
    ..Another important target in AD is the neurofibrillary tangles and its precursors, composed primarily of hyperphosphorylated tau proteins, which correlate well with the ..
  46. Yuzwa S, Vocadlo D. O-GlcNAc modification and the tauopathies: insights from chemical biology. Curr Alzheimer Res. 2009;6:451-4 pubmed
    ..In this mini-review, we highlight the use of chemical compounds as a means of understanding the reciprocal nature of tau phosphorylation and tau O-GlcNAcylation and highlight some recent progress in this area. ..
  47. Alafuzoff I, Arzberger T, Al Sarraj S, Bodi I, Bogdanovic N, Braak H, et al. Staging of neurofibrillary pathology in Alzheimer's disease: a study of the BrainNet Europe Consortium. Brain Pathol. 2008;18:484-96 pubmed publisher
    ..Thus, in a research setting when the extent of lesions is mild, it is strongly recommended that the assessment of lesions should be carried out by at least two independent observers. ..
  48. Oddo S, Caccamo A, Cheng D, LaFerla F. Genetically altering Abeta distribution from the brain to the vasculature ameliorates tau pathology. Brain Pathol. 2009;19:421-30 pubmed publisher
    ..The 3xTg-AD mice expressing the human apoE4 gene were virtually depleted of any somatodendritic tau deposits. These data strongly suggest that the somatodendritic tau accumulation is dependent on the parenchyma Abeta deposits. ..
  49. Rosen R, Farberg A, Gearing M, Dooyema J, Long P, Anderson D, et al. Tauopathy with paired helical filaments in an aged chimpanzee. J Comp Neurol. 2008;509:259-70 pubmed publisher
    ..Ultrastructurally, the neurofibrillary tangles consisted of tau-immunoreactive paired helical filaments with a diameter and helical periodicity ..
  50. Koson P, Zilka N, Kovac A, Kovacech B, Korenova M, Filipcik P, et al. Truncated tau expression levels determine life span of a rat model of tauopathy without causing neuronal loss or correlating with terminal neurofibrillary tangle load. Eur J Neurosci. 2008;28:239-46 pubmed publisher
    ..the impact of truncated tau expression levels on life span, neuronal loss and the final load of neurofibrillary tangles (NFTs) in transgenic rats...
  51. Takashima A. Hyperphosphorylated tau is a cause of neuronal dysfunction in tauopathy. J Alzheimers Dis. 2008;14:371-5 pubmed
    Pathological studies show that neurofibrillary tangles are found in regions where neuronal death occurs...
  52. Simic G, Stanic G, Mladinov M, Jovanov Milosevic N, Kostovic I, Hof P. Does Alzheimer's disease begin in the brainstem?. Neuropathol Appl Neurobiol. 2009;35:532-54 pubmed publisher
    ..Within such a framework, beta-amyloid production is considered only as one of the factors (although a significant one in familial cases) that promotes molecular series of events underlying AD-related neuropathological changes. ..
  53. Schneider A, Mandelkow E. Tau-based treatment strategies in neurodegenerative diseases. Neurotherapeutics. 2008;5:443-57 pubmed publisher
    b>Neurofibrillary tangles are a characteristic hallmark of Alzheimer's and other neurodegenerative diseases, such as Pick's disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal dementia ..