Neuronal Trafficking in Aging

Claudia Almeida2

Cláudia Almeida

Principal Investigator

CV 2018



Campus Sant'Ana
Pólo de Investigação, NMS, UNL
Rua Câmara Pestana, nº 6
Lab 2.7
1150-082 Lisboa, Portugal

Lab 2.07 | Office 2.27

Phone: +351 218803101, Ext.:26010
Lab Ext: 26053
E-mail: claudia.almeida(at)



Main interests

app bace1 trafficking-02-02

Alzheimer’s disease (AD) is the most frequent synaptic disorder of the increasingly aging population. It is uncertain if the current therapeutic strategies based on late disease events and on research on familial forms of AD (fAD) will benefit the 99% of AD patients with unknown etiology. The late onset AD etiology is likely multifactorial, with aging being the biggest risk factor and genetic predisposition likely accelerating the disease onset.
The lack of successful therapies is in part due to the irreversible neurodegeneration already installed in the affected patients. We have shown that early synaptic dysfunction is a major reversible target (Almeida et. Al, 2005; Snyder et-al 20015).
Now our focus is to determine the causal mechanisms of synaptic dysfunction in the common Late-onset Alzheimer’s disease (LOAD). Aging is the main risk factor for AD, but the contribution of intrinsic neuronal aging to LOAD is unkown. Several endocytic regulators were identified as LOAD genetic risk factors indicating endolysosomal dysfunction as a major cellular AD mechanism however how it contributes to LOAD is unclear.
Thus, we hypothesize that neuronal endolysosomal dysfunction, either by aging or genetic risk factors, contributes to synaptic dysfunction in LOAD.

Research Areas

Our aims are:
1. Does deregulation of endosomal sorting drive synaptic dysfunction?
BIN1 and CD2AP, two top ten GWAS genes are regulators of endosomal trafficking and actin dynamics(20, 28). We found that Bin1 and CD2AP loss of function increase endogenous Aβ production(21). We showed that both enhance APP access to β- and γ-secretases at sorting endosomes by distinct mechanisms of endosomal sorting(21).
We are investigating the impact of AD variants in Bin1 and CD2AP on intraneuronal Aβ42 by semi-quantitative single cell immunofluorescence, on APP and its secretases trafficking by pulse-chase assays, morphological and molecular analysis using imaging and biochemistry assays using mouse primary neurons, or alternatively in Neuro2a cell line we are developing in collaboration with C. Brito (iBET) induced human neurons edited with AD variants using Crispr/CAS9 in collaboration with A. Gontijo (CEDOC).

2. Does neuronal endocytic trafficking become dysfunctional with neuronal aging and have an impact on synapses?
Multiple mechanisms intrinsic to aging neurons likely drive synaptic decline. We are investigating investigate how age-related endocytic trafficking dysfunction drives aging-synaptic decline using in mouse primary neurons aged in vitro.
Overall, we aim to identify novel cellular and molecular mechanisms that deregulate the endolysosomal pathway in normal aging and upon LOAD genetic risk, establishing causality between aging and genetic variants and the development of LOAD.
Ultimately, we hope to determine the mechanisms underlying synaptic decline in aging neurons to identify novel therapeutic targets to delay or prevent AD.

synapses neuron

Discover more about the Neuronal Trafficking in Aging Lab

- À procura do segredo da longevidade

endosomes neuron



2019-2022 Understanding the Impact of a Late-Onset Alzheimer's Disease Mutation in CD2AP on Synapses
Alzheimer's Association
PI: Cláudia G. Almeida

2018-2022 LYSOCIL: Excel in Rare Diseases’ Research: Focus on LYSOsomal Disorders and CILiopathies
European Union’s Horizon Twinning project 2020 (No 811087)
Partner: Cláudia G. Almeida

2018 Impact of the genetic risk factor CD2AP on the development of Alzheimer's disease
CO-PI: Cláudia G. Almeida

2017 Impact of the genetic risk factor CD2AP on the development of Alzheimer's disease
Award Maratona da Saúde
PI: Cláudia G. Almeida

2016-2019 NAB3
Cofund JPND/H2020
Partner: Cláudia G. Almeida

2015 Recapitulating late-onset Alzheimer’s disease in a three dimensional human neural cell model
Award Santander/Totta and Universidade NOVA de Lisboa
PI: Cláudia G. Almeida

2013-2017 Marie Curie Integration grant - TrafficInAD
Marie Curie Actions, EC
PI: Cláudia G. Almeida

2013 - 2018 Investigador FCT exploratory project
Foundation for Science and Technology, Portugal
PI: Cláudia G. Almeida

2013 - 2016 Imaging the structure and dynamics of molecules and complexes in living organisms
Foundation for Science and Technology, Portugal
PI: Nuno Moreno, Partner: Cláudia G. Almeida

  • Almeida CG, Yamada A, Tenza D, Louvard D, Raposo G, Coudrier E. Myosin 1b promotes the formation of post-Golgi carriers by regulating actin assembly and membrane remodelling at the trans-Golgi network. Nat Cell Bio. 2011, Jun 12;13(7):779-89. (10 citations; IF = 19.407)
  • Tampellini D, Magrane J, Takahashi RH, Li F, Lin MT, Almeida CG, Gouras GK. Internalized Antibodies to the Abeta Domain of APP Reduce Neuronal Abeta and Protect against Synaptic Alterations. J Biol Chem. 2007 Jun 29;282(26):18895-906. (61 citations; IF = 3.603)
  • Sahlin C, Lord A, Magnusson K, Englund H, Almeida CG, Greengard P, Nyberg F, Gouras GK, Lannfelt L, Nilsson LN. The Arctic Alzheimer mutation favors intracellular amyloid-beta production by making amyloid precursor protein less available to alpha-secretase. J Neurochem. 2007 May;101(3):854-62. (22 citations; IF = 4.337)
  • Almeida CG, Takahashi RH, Gouras GK. Aβ42 accumulation impairs multivesicular body sorting by inhibiting the ubiquitin-proteasome system. J Neuroscience. Apr 19;26(16):4277-88. (90 citations; IF = 7.271)
  • Almeida CG, Tampellini D, Takahashi RH, Greengard P, Lin MT, Snyder EM, Gouras GK. Beta-amyloid accumulation in APP mutant neurons reduces PSD-95 and GluR1 in synapses. Neurobiol Dis. 2005 Nov;20(2):187-98 (145 citations; IF = 5.121)
  • Snyder EM, Nong Y, Almeida CG, Paul S, Moran T, Choi EY, Nairn AC, Salter MW, Lombroso PJ, Gouras GK, Greengard P. Regulation of NMDA receptor trafficking by amyloid-beta. Nat Neurosci. 2005 Aug;8(8):1051-8. (551 citations; IF = 14.191)
  • Gouras GK, Almeida CG, Takahashi RH. Intraneuronal Abeta accumulation and origin of plaques in Alzheimer's disease. Neurobiol Aging. 2005 Oct;26(9):1235-44. (125 citations; IF = 6.634)
  • Stenh C, Englund H, Lord A, Johansson AS, Almeida CG, Gellerfors P, Greengard P, Gouras GK, Lannfelt L, Nilsson LN. Amyloid-beta oligomers are inefficiently measured by enzyme-linked immunosorbent assay. Ann Neurol. 2005 Jul;58(1):147-50. (48 citations; IF = 10.746)
  • Li F, Calingasan NY, Yu F, Mauck WM, Toidze M, Almeida CG, Takahashi RH, Carlson GA, Flint Beal M, Lin MT, Gouras GK. Increased plaque burden in brains of APP mutant MnSOD heterozygous knockout mice.J Neurochem. 2004 Jun;89(5):1308-12. (110 citations; IF = 4.337)
  • Takahashi RH, Almeida CG, Kearney PF, Yu F, Lin MT, Milner TA, Gouras GK. Oligomerization of Alzheimer's beta-amyloid within processes and synapses of cultured neurons and brain. J Neurosci. 2004 Apr 7;24(14):3592-9. (211 citations; IF = 7.271)
  • Almeida CG, de Mendonca A., Cunha R.A., Ribeiro J.A. “Adenosine promotes neuronal recovery from reactive oxygen species induced lesion in rat hippocampal slices”. Neurosci Lett. 2003 339:127-30. (25 citations; IF = 2.055)


- Catarina Brito, ITQB

- Tiago Gil Oliveira, ICVS | 3B's

- Orfeu Flores, STAB Vida

- Henrique Girão, IBILI

Team photos

Lab CAlmeida_2018






CEDO IGC   12-6-2013 - 7406

1 Post-Doctoral Research Fellowship @ Cláudia's Almeida Lab

An international call for one postdoctoral research fellowship under the project entitled “Understanding the Impact of a Late-Onset Alzheimer's Disease Mutation in CD2AP on Synapses", at Neuronal trafficking in aging Lab, under the supervision and mentoring of Cláudia Guimas Almeida, at the Center of Chronic Diseases Research – CEDOC of the NOVA Medical School | Universidade NOVA de Lisboa of Lisbon, is open.

The Postdoctoral Researcher will develop a novel cellular model of late-onset Alzheimeir’s disease using human neurons differentiated from hIPSCs edited with CrisPR-CAS9 with the patient’s mutations, to evaluate how Alzheimer’s late-onset mutations disrupt neuronal function.
Candidates must hold a PhD in Neurosciences or equivalent (PhD defended in the last 3 months or to be defended until the end of April). Failure to meet these requirements is sufficient to exclude candidates.

The call is open from February 23 to March 8, 2021 and applications must be sent by email to, mentioning the reference of Bolsa DAI / 2021/05 in the subject.

Know more about this position here.