This is a most interesting paper. Inadequate clearance of Aβ from the brain is considered to play a critical role in amyloid accumulation of late-onset Alzheimer's disease (LOAD). Despite the research efforts of the last three decades, the role of the lymphatic system in amyloid clearance has been largely ignored. The brain lacks lymphatic channels; however, as Dr. Pappolla emphasizes in this study, circulation of immune-competent cells, such as dendritic and perivascular cells, between brain and peripheral lymph nodes is well established. A role for glymphatic interstitial fluid (ISF) bulk flow clearance, which drains into the peripheral lymphatics, in regulating brain Aß levels, is being recognized (Iliff JJ et al., 2013). The glymphatic system is the brain's version of the peripheral lymphatic system. Peripheral lymph nodes participate in immune surveillance and antigen presentation in the brain, particularly during neuro-inflammatory processes. Recently, a substantial number of new genes that associate with increased risk of AD has been discovered. Because the products of many of these genes are involved in immune modulatory functions, the study by Pappolla et al. highlights a new perspective in AD pathogenesis, which may have significant therapeutic impact in this disease. Our own recent studies have shown that stimulation of the innate immune system can reduce both Aβ and tau pathology, consistent with this being an important therapeutic target (Scholtzova et al., 2014).
References:
Iliff JJ, Nedergaard M.
Is there a cerebral lymphatic system?.
Stroke. 2013 Jun;44(6 Suppl 1):S93-5.
PubMed.
Scholtzova H, Chianchiano P, Pan J, Sun Y, Goñi F, Mehta PD, Wisniewski T.
Amyloid β and Tau Alzheimer's disease related pathology is reduced by Toll-like receptor 9 stimulation.
Acta Neuropathol Commun. 2014 Sep 2;2:101.
PubMed.
This is a very important paper from Dr. Pappolla and associates. It demonstrates for the first time that the lymphatic system may play a substantive role in the clearance of Aβ peptides from the brain. Impaired clearance of amyloid may play a major role in amyloid accumulation in the brain. Thus far, research on amyloid clearance has been focused on the blood brain barrier while the role of the lymphatic system may have been overlooked. Dr. Pappolla's paper brings attention to a potentially important mechanism for amyloid accumulation that may bear significant pathogenic implications for Alzheimer's disease.
Comments
New York University
This is a most interesting paper. Inadequate clearance of Aβ from the brain is considered to play a critical role in amyloid accumulation of late-onset Alzheimer's disease (LOAD). Despite the research efforts of the last three decades, the role of the lymphatic system in amyloid clearance has been largely ignored. The brain lacks lymphatic channels; however, as Dr. Pappolla emphasizes in this study, circulation of immune-competent cells, such as dendritic and perivascular cells, between brain and peripheral lymph nodes is well established. A role for glymphatic interstitial fluid (ISF) bulk flow clearance, which drains into the peripheral lymphatics, in regulating brain Aß levels, is being recognized (Iliff JJ et al., 2013). The glymphatic system is the brain's version of the peripheral lymphatic system. Peripheral lymph nodes participate in immune surveillance and antigen presentation in the brain, particularly during neuro-inflammatory processes. Recently, a substantial number of new genes that associate with increased risk of AD has been discovered. Because the products of many of these genes are involved in immune modulatory functions, the study by Pappolla et al. highlights a new perspective in AD pathogenesis, which may have significant therapeutic impact in this disease. Our own recent studies have shown that stimulation of the innate immune system can reduce both Aβ and tau pathology, consistent with this being an important therapeutic target (Scholtzova et al., 2014).
References:
Iliff JJ, Nedergaard M. Is there a cerebral lymphatic system?. Stroke. 2013 Jun;44(6 Suppl 1):S93-5. PubMed.
Scholtzova H, Chianchiano P, Pan J, Sun Y, Goñi F, Mehta PD, Wisniewski T. Amyloid β and Tau Alzheimer's disease related pathology is reduced by Toll-like receptor 9 stimulation. Acta Neuropathol Commun. 2014 Sep 2;2:101. PubMed.
Mount Sinai School of Medicine, NYU
This is a very important paper from Dr. Pappolla and associates. It demonstrates for the first time that the lymphatic system may play a substantive role in the clearance of Aβ peptides from the brain. Impaired clearance of amyloid may play a major role in amyloid accumulation in the brain. Thus far, research on amyloid clearance has been focused on the blood brain barrier while the role of the lymphatic system may have been overlooked. Dr. Pappolla's paper brings attention to a potentially important mechanism for amyloid accumulation that may bear significant pathogenic implications for Alzheimer's disease.
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